MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Developmental Cell' source. Tue, 07 Feb 2012 08:48:56 +0100 http://www.medworm.com/index.php?rid=5640324&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280890%26dopt%3DAbstract Authors: Yue T, Tian A, Jiang J Abstract The Hippo (Hpo) signaling pathway controls tissue growth and organ size in species ranging from Drosophila to mammals and is deregulated in a wide range of human cancers. The core pathway consists of the Hpo/Warts (Wts) kinase cassette that phosphorylates and inactivates the transcriptional coactivator Yorkie (Yki). Here, we report that Echinoid (Ed), an immunoglobulin domain-containing cell adhesion molecule, acts as an upstream regulator of the Hpo pathway. Loss of Ed compromises Yki phosphorylation, resulting in elevated Yki activity that increases Hpo target gene expression and drives tissue overgrowth. Ed physically interacts with and stabilizes the Hpo-binding partner Salvador (Sav) at adherens junctions. Ed/Sav interaction is promote... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5640324 Tue, 24 Jan 2012 05:00:00 +0100 5640324 http://www.medworm.com/index.php?rid=5640323&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280891%26dopt%3DAbstract Authors: Lazarou M, Jin SM, Kane LA, Youle RJ Abstract Mutations in the mitochondrial kinase PINK1 and the cytosolic E3 ligase Parkin can cause Parkinson's disease. Damaged mitochondria accumulate PINK1 on the outer membrane where, dependent on kinase activity, it recruits and activates Parkin to induce mitophagy, potentially maintaining organelle fidelity. How PINK1 recruits Parkin is unknown. We show that endogenous PINK1 forms a 700 kDa complex with the translocase of the outer membrane (TOM) selectively on depolarized mitochondria whereas PINK1 ectopically targeted to the outer membrane retains association with TOM on polarized mitochondria. Inducibly targeting PINK1 to peroxisomes or lysosomes, which lack a TOM complex, recruits Parkin and activates ubiquitin ligase activity ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5640323 Tue, 24 Jan 2012 05:00:00 +0100 5640323 http://www.medworm.com/index.php?rid=5623361&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264801%26dopt%3DAbstract Authors: Han SM, Tsuda H, Yang Y, Vibbert J, Cottee P, Lee SJ, Winek J, Haueter C, Bellen HJ, Miller MA Abstract The VAPB/ALS8 major sperm protein domain (vMSP) is implicated in amyotrophic lateral sclerosis and spinal muscular atrophy, yet its function in the nervous system is not well understood. In Caenorhabditis elegans and Drosophila, the vMSP is cleaved from its transmembrane anchor and secreted in a cell type-specific fashion. We show that vMSPs secreted by neurons act on Lar-like protein-tyrosine phosphatase and Roundabout growth cone guidance receptors expressed in striated muscle. This signaling pathway promotes Arp2/3-dependent actin remodeling and mitochondrial localization to actin-rich muscle I-bands. C. elegans VAPB mutants have mitochondrial localization, morphol... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623361 Wed, 18 Jan 2012 05:00:00 +0100 5623361 http://www.medworm.com/index.php?rid=5623360&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264802%26dopt%3DAbstract Authors: D'Angelo MA, Gomez-Cavazos JS, Mei A, Lackner DH, Hetzer MW Abstract Nuclear pore complexes (NPCs) are built from ∼30 different proteins called nucleoporins or Nups. Previous studies have shown that several Nups exhibit cell-type-specific expression and that mutations in NPC components result in tissue-specific diseases. Here we show that a specific change in NPC composition is required for both myogenic and neuronal differentiation. The transmembrane nucleoporin Nup210 is absent in proliferating myoblasts and embryonic stem cells (ESCs) but becomes expressed and incorporated into NPCs during cell differentiation. Preventing Nup210 production by RNAi blocks myogenesis and the differentiation of ESCs into neuroprogenitors. We found that the addition of Nup210 to NPCs does... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623360 Wed, 18 Jan 2012 05:00:00 +0100 5623360 http://www.medworm.com/index.php?rid=5623373&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264723%26dopt%3DAbstract Authors: Stimpson KM, Sullivan BA Abstract Eukaryotic centromeres are propagated by incorporation of the centromere-specific histone CENP-A into centromeric chromatin. Silva et al. (2012) now show that cyclin-dependent kinases (CDKs) hold the CENP-A assembly machinery in an inactive state until mitotic exit and entry into G1, at which time new CENP-A is loaded. PMID: 22264723 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623373 Tue, 17 Jan 2012 05:00:00 +0100 5623373 http://www.medworm.com/index.php?rid=5623372&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264724%26dopt%3DAbstract Authors: Behrndt M, Heisenberg CP Abstract How cells orchestrate their behavior during collective migration is a long-standing question. Using magnetic tweezers to apply mechanical stimuli to Xenopus mesendoderm cells, Weber et al. (2012) now reveal, in this issue of Developmental Cell, a cadherin-mediated mechanosensitive response that promotes cell polarization and movement persistence during the collective mesendoderm migration in gastrulation. PMID: 22264724 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623372 Tue, 17 Jan 2012 05:00:00 +0100 5623372 http://www.medworm.com/index.php?rid=5623371&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264725%26dopt%3DAbstract Contact is repulsive, but please note the "enclosed". Dev Cell. 2012 Jan 17;22(1):5-6 Authors: Burgess RW, Garrett AM, Tadenev AL Abstract Previous models of neuronal dendrite arborization suggested that contact-dependent self-avoidance between dendrite branches prevents self-crossings within the arbor. Two papers in Neuron show how integrin-mediated adhesion to the extracellular matrix restricts dendrites to a two-dimensional space to optimize this mechanism (Han et al., 2012; Kim et al., 2012). PMID: 22264725 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623371 Tue, 17 Jan 2012 05:00:00 +0100 5623371 http://www.medworm.com/index.php?rid=5623370&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264726%26dopt%3DAbstract Authors: Lyons DA, Talbot WS Abstract A recent Neuron paper by Zhang et al. (2012) reveals how ion channels and adhesion molecules essential for rapid nerve conduction in vertebrates are differentially targeted to nodes of Ranvier. Moreover, distinct mechanisms regulate initial clustering and maintenance of specific nodal components. PMID: 22264726 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623370 Tue, 17 Jan 2012 05:00:00 +0100 5623370 http://www.medworm.com/index.php?rid=5623369&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264727%26dopt%3DAbstract Authors: Lenhard M Abstract The transition from cell proliferation to cell expansion is critical for determining leaf size. Andriankaja et al. (2012) demonstrate that in leaves of dicotyledonous plants, a basal proliferation zone is maintained for several days before abruptly disappearing, and that chloroplast differentiation is required to trigger the onset of cell expansion. PMID: 22264727 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623369 Tue, 17 Jan 2012 05:00:00 +0100 5623369 http://www.medworm.com/index.php?rid=5623368&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264728%26dopt%3DAbstract Authors: Bilder D, Haigo SL Abstract Tissue and organ architectures are incredibly diverse, yet our knowledge of the morphogenetic behaviors that generate them is relatively limited. Recent studies have revealed unexpected mechanisms that drive axis elongation in the Drosophila egg, including an unconventional planar polarity signaling pathway, a distinctive type of morphogenetic movement termed "global tissue rotation," a molecular corset-like role of extracellular matrix, and oscillating basal cellular contractions. We review here what is known about Drosophila egg elongation, compare it to other instances of morphogenesis, and highlight several issues of general developmental relevance. PMID: 22264728 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623368 Tue, 17 Jan 2012 05:00:00 +0100 5623368 http://www.medworm.com/index.php?rid=5623367&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264729%26dopt%3DAbstract Authors: Yan J, Mihaylov V, Xu X, Brzostowski JA, Li H, Liu L, Veenstra TD, Parent CA, Jin T Abstract Activation of G protein-coupled receptors (GPCRs) leads to the dissociation of heterotrimeric G-proteins into Gα and Gβγ subunits, which go on to regulate various effectors involved in a panoply of cellular responses. During chemotaxis, Gβγ subunits regulate actin assembly and migration, but the protein(s) linking Gβγ to the actin cytoskeleton remains unknown. Here, we identified a Gβγ effector, ElmoE in Dictyostelium, and demonstrated that it is required for GPCR-mediated chemotaxis. Remarkably, ElmoE associates with Gβγ and Dock-like proteins to activate the small GTPase Rac, in a GPCR-dependent manner, and also associates with Arp2/3 complex and F-actin. Thus, ElmoE s... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623367 Tue, 17 Jan 2012 05:00:00 +0100 5623367 http://www.medworm.com/index.php?rid=5623366&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264730%26dopt%3DAbstract Authors: Thapa N, Sun Y, Schramp M, Choi S, Ling K, Anderson RA Abstract Polarized delivery of signaling and adhesion molecules to the leading edge is required for directional migration of cells. Here, we describe a role for the PIP(2)-synthesizing enzyme, PIPKIγi2, in regulation of exocyst complex control of cell polarity and polarized integrin trafficking during migration. Loss of PIPKIγi2 impaired directional migration, formation of cell polarity, and integrin trafficking to the leading edge. Upon initiation of directional migration, PIPKIγi2 via PIP(2) generation controls the integration of the exocyst complex into an integrin-containing trafficking compartment that requires the talin-binding ability of PIPKIγi2, and talin for integrin recruitment to the leading edge. A PIP... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623366 Tue, 17 Jan 2012 05:00:00 +0100 5623366 http://www.medworm.com/index.php?rid=5623365&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264731%26dopt%3DAbstract Authors: Chen XL, Nam JO, Jean C, Lawson C, Walsh CT, Goka E, Lim ST, Tomar A, Tancioni I, Uryu S, Guan JL, Acevedo LM, Weis SM, Cheresh DA, Schlaepfer DD Abstract Endothelial cells (ECs) form cell-cell adhesive junctional structures maintaining vascular integrity. This barrier is dynamically regulated by vascular endothelial growth factor (VEGF) receptor signaling. We created an inducible knockin mouse model to study the contribution of the integrin-associated focal adhesion tyrosine kinase (FAK) signaling on vascular function. Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation, rapid FAK localization to cell... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623365 Tue, 17 Jan 2012 05:00:00 +0100 5623365 http://www.medworm.com/index.php?rid=5623364&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264732%26dopt%3DAbstract In this study, we investigate flies lacking PRAS40. Surprisingly, we find both biochemically and genetically that PRAS40 couples IIS to TORC1 activation in a tissue-specific manner, regulating TORC1 activity in ovaries but not in other tissues of the animal. PRAS40 thereby regulates fertility but not growth of the fly, allowing distinct physiological functions of TORC1 to be uncoupled. We also show that the main function of PRAS40 in vivo is to regulate TORC1 activity, and not to act as a downstream target and effector of TORC1. Finally, this work sheds some light on the question of whether TORC1 activity is coupled to IIS in vivo. PMID: 22264732 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623364 Tue, 17 Jan 2012 05:00:00 +0100 5623364 http://www.medworm.com/index.php?rid=5623363&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264733%26dopt%3DAbstract Authors: Rademacher EH, Lokerse AS, Schlereth A, Llavata-Peris CI, Bayer M, Kientz M, Freire Rios A, Borst JW, Lukowitz W, Jürgens G, Weijers D Abstract The cell types of the plant root are first specified early during embryogenesis and are maintained throughout plant life. Auxin plays an essential role in embryonic root initiation, in part through the action of the ARF5/MP transcription factor and its auxin-labile inhibitor IAA12/BDL. MP and BDL function in embryonic cells but promote auxin transport to adjacent extraembryonic suspensor cells, including the quiescent center precursor (hypophysis). Here we show that a cell-autonomous auxin response within this cell is required for root meristem initiation. ARF9 and redundant ARFs, and their inhibitor IAA10, act in suspensor cells... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623363 Tue, 17 Jan 2012 05:00:00 +0100 5623363 http://www.medworm.com/index.php?rid=5623362&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22264734%26dopt%3DAbstract Authors: Martin BL, Kimelman D Abstract The vertebrate body forms in an anterior-to-posterior progression, driven by a population of undifferentiated cells at the posterior-most end of the embryo. Recent studies have demonstrated that these undifferentiated cells are multipotent stem cells, suggesting that local signaling factors specify cell fate. However, the mechanism of cell fate specification during this process is unknown. Using a combination of single cell transplantation and newly developed cell-autonomous inducible Wnt inhibitor and activator transgenic zebrafish lines, we show that canonical Wnt signaling is continuously necessary and sufficient to specify mesoderm from a bipotential neural/mesodermal precursor. Surprisingly, we also find that Wnt signaling functions subs... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5623362 Tue, 17 Jan 2012 05:00:00 +0100 5623362 http://www.medworm.com/index.php?rid=5578599&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227309%26dopt%3DAbstract Authors: Lee HK, Deneen B Abstract The Daam family of proteins consists of Daam1 and Daam2. Although Daam1 participates in noncanonical Wnt signaling during gastrulation, Daam2 function remains completely uncharacterized. Here we describe the role of Daam2 in canonical Wnt signal transduction during spinal cord development. Loss-of-function studies revealed that Daam2 is required for dorsal progenitor identities and canonical Wnt signaling. These phenotypes are rescued by β-catenin, demonstrating that Daam2 functions in dorsal patterning through the canonical Wnt pathway. Complementary gain-of-function studies demonstrate that Daam2 amplifies Wnt signaling by potentiating ligand activation. Biochemical examination found that Daam2 association with Dvl3 is required for Wnt activity... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5578599 Wed, 04 Jan 2012 05:00:00 +0100 5578599 http://www.medworm.com/index.php?rid=5578598&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22227310%26dopt%3DAbstract Authors: Andriankaja M, Dhondt S, De Bodt S, Vanhaeren H, Coppens F, De Milde L, Mühlenbock P, Skirycz A, Gonzalez N, Beemster GT, Inzé D Abstract Early leaf growth is sustained by cell proliferation and subsequent cell expansion that initiates at the leaf tip and proceeds in a basipetal direction. Using detailed kinematic and gene expression studies to map these stages during early development of the third leaf of Arabidopsis thaliana, we showed that the cell-cycle arrest front did not progress gradually down the leaf, but rather was established and abolished abruptly. Interestingly, leaf greening and stomatal patterning followed a similar basipetal pattern, but proliferative pavement cell and formative meristemoid divisions were uncoordinated in respect to onset and persisten... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5578598 Wed, 04 Jan 2012 05:00:00 +0100 5578598 http://www.medworm.com/index.php?rid=5578601&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209328%26dopt%3DAbstract Authors: Geng LN, Yao Z, Snider L, Fong AP, Cech JN, Young JM, van der Maarel SM, Ruzzo WL, Gentleman RC, Tawil R, Tapscott SJ Abstract Facioscapulohumeral dystrophy (FSHD) is one of the most common inherited muscular dystrophies. The causative gene remains controversial and the mechanism of pathophysiology unknown. Here we identify genes associated with germline and early stem cell development as targets of the DUX4 transcription factor, a leading candidate gene for FSHD. The genes regulated by DUX4 are reliably detected in FSHD muscle but not in controls, providing direct support for the model that misexpression of DUX4 is a causal factor for FSHD. Additionally, we show that DUX4 binds and activates LTR elements from a class of MaLR endogenous primate retrotransposons and suppre... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5578601 Wed, 28 Dec 2011 05:00:00 +0100 5578601 http://www.medworm.com/index.php?rid=5578600&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209329%26dopt%3DAbstract Authors: Wimmer R, Cseh B, Maier B, Scherrer K, Baccarini M Abstract Sprouting angiogenesis, crucial for the development of new blood vessels, is a prime example of collective migration in which endothelial cells migrate as a group joined via cadherin-containing adherens junctions (AJ). The actomyosin apparatus is connected to AJ and generates contractile forces, which, depending on their strength and duration, increase or decrease cell cohesion. Thus, appropriate spatiotemporal control of junctional myosin is critical, but the mechanisms underlying it are incompletely understood. We show that Raf-1 is an essential component of this regulatory network and that its ablation impairs endothelial cell cohesion, sprouting, and tumor-induced angiogenesis. Mechanistically, Raf-1 is recr... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5578600 Wed, 28 Dec 2011 05:00:00 +0100 5578600 http://www.medworm.com/index.php?rid=5550450&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192413%26dopt%3DAbstract Authors: Lee S, Lee JW, Lee SK Abstract The removal of histone H3 lysine27 (H3K27) trimethylation mark is important for the robust induction of many cell type-specific genes during differentiation. Here we show that UTX, a H3K27 demethylase, acts as a critical switch to promote a cardiac-specific gene program. UTX-deficient ESCs failed to develop heart-like rhythmic contractions under a cardiac differentiation condition. UTX-deficient mice show severe defects in heart development and embryonic lethality. We found that UTX is recruited to cardiac-specific enhancers by associating with core cardiac transcription factors and demethylates H3K27 residues in cardiac genes. In addition, UTX facilitates the recruitment of Brg1 to the cardiac-specific enhancers. Together, our data reveal ke... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5550450 Tue, 20 Dec 2011 05:00:00 +0100 5550450 http://www.medworm.com/index.php?rid=5550449&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22197222%26dopt%3DAbstract Authors: Dozynkiewicz MA, Jamieson NB, Macpherson I, Grindlay J, van den Berghe PV, von Thun A, Morton JP, Gourley C, Timpson P, Nixon C, McKay CJ, Carter R, Strachan D, Anderson K, Sansom OJ, Caswell PT, Norman JC Abstract Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches show that lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells and tumors, which colocalizes with active α5β1 in late endosomes/lysosomes. CLIC3 is necessary for release of the cell rear during migration on 3D matrices and is requ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5550449 Tue, 20 Dec 2011 05:00:00 +0100 5550449 http://www.medworm.com/index.php?rid=5535371&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178499%26dopt%3DAbstract Authors: Yoshiura S, Ohta N, Matsuzaki F Abstract During development, directional cell division is a major mechanism for establishing the orientation of tissue growth. Drosophila neuroblasts undergo asymmetric divisions perpendicular to the overlying epithelium to produce descendant neurons on the opposite side, thereby orienting initial neural tissue growth. However, the mechanism remains elusive. We provide genetic evidence that extrinsic GPCR signaling determines the orientation of cortical polarity underlying asymmetric divisions of neuroblasts relative to the epithelium. The GPCR Tre1 activates the G protein oα subunit in neuroblasts by interacting with the epithelium to recruit Pins, which regulates spindle orientation. Because Pins associates with the Par-complex via Inscut... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5535371 Wed, 14 Dec 2011 05:00:00 +0100 5535371 http://www.medworm.com/index.php?rid=5535370&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178500%26dopt%3DAbstract Authors: Merrick D, Chapin H, Baggs JE, Yu Z, Somlo S, Sun Z, Hogenesch JB, Caplan MJ Abstract Mutations in Pkd1, encoding polycystin-1 (PC1), cause autosomal-dominant polycystic kidney disease (ADPKD). We show that the carboxy-terminal tail (CTT) of PC1 is released by γ-secretase-mediated cleavage and regulates the Wnt and CHOP pathways by binding the transcription factors TCF and CHOP, disrupting their interaction with the common transcriptional coactivator p300. Loss of PC1 causes increased proliferation and apoptosis, while reintroducing PC1-CTT into cultured Pkd1 null cells reestablishes normal growth rate, suppresses apoptosis, and prevents cyst formation. Inhibition of γ-secretase activity impairs the ability of PC1 to suppress growth and apoptosis and leads to cyst format... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5535370 Wed, 14 Dec 2011 05:00:00 +0100 5535370 http://www.medworm.com/index.php?rid=5513818&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172664%26dopt%3DAbstract Authors: Blythe SA, Klein PS Abstract Recent work has raised the possibility that chromatin modifications pre-set embryonic patterns of gene expression. In this issue of Developmental Cell, Lindeman et al. (2011) support this observation and describe how the pattern of several chromatin marks evolves over the transition from maternal to zygotic control of development. PMID: 22172664 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513818 Tue, 13 Dec 2011 05:00:00 +0100 5513818 http://www.medworm.com/index.php?rid=5513817&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172665%26dopt%3DAbstract Authors: Hamilton BA, Fu XD Abstract Are all introns spliced cotranscriptionally? In a recent issue of Cell, Vargas et al. (2011) reported single-molecule analyses of pre-mRNA splicing, confirming transcription-coupled splicing of constitutive introns but finding off-site and delayed splicing of alternative introns. The results raise the question of whether kinetics distinguishes constitutive from regulated splicing. PMID: 22172665 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513817 Tue, 13 Dec 2011 05:00:00 +0100 5513817 http://www.medworm.com/index.php?rid=5513816&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172666%26dopt%3DAbstract Authors: Bastock R, St Johnston D Abstract The entry of the sperm centrosome polarizes the anterior-posterior axis of the C. elegans zygote by inducing the formation of complementary cortical Par protein domains. Recent papers from the Seydoux and Grill laboratories (Goehring et al., 2011b and Motegi et al., 2011) reveal how two different symmetry-breaking mechanisms produce the same final pattern through interactions between Par proteins. PMID: 22172666 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513816 Tue, 13 Dec 2011 05:00:00 +0100 5513816 http://www.medworm.com/index.php?rid=5513815&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172667%26dopt%3DAbstract Authors: Lim J, Thiery JP Abstract The epithelial-to-mesenchymal transition (EMT), a key process in morphogenesis, is often driven by repressing expression of adherens junction components, such as E-cadherin. In this issue of Developmental Cell, Campbell et al. (2011) uncover an alternative mechanism in the Drosophila embryonic gut that promotes EMT via Serpent, a GATA transcriptional repressor of the apicobasal polarity gene crumbs. PMID: 22172667 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513815 Tue, 13 Dec 2011 05:00:00 +0100 5513815 http://www.medworm.com/index.php?rid=5513814&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172668%26dopt%3DAbstract Authors: Vert G, Chory J Abstract During the past two decades, molecular biologists and geneticists have deconstructed intracellular signaling pathways in individual cells, revealing a great deal of crosstalk among key signaling pathways in the animal kingdom. Fewer examples have been reported in plants, which appear to integrate multiple signals on the promoters of target genes or to use gene family members to convey signal-specific output. For both plants and animals, the question now is whether the "crosstalk" is biologically relevant or simply noise in the experimental system. To minimize such noise, we suggest studying signaling pathways in the context of intact organisms with minimal perturbation from the experimenter. PMID: 22172668 [PubMed - in process] (Source: Develop... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513814 Tue, 13 Dec 2011 05:00:00 +0100 5513814 http://www.medworm.com/index.php?rid=5513813&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172669%26dopt%3DAbstract Authors: Frankenberg S, Gerbe F, Bessonnard S, Belville C, Pouchin P, Bardot O, Chazaud C Abstract During preimplantation mouse development, the inner cell mass (ICM) differentiates into two cell lineages-the epiblast and the primitive endoderm (PrE)-whose precursors are identifiable by reciprocal expression of Nanog and Gata6, respectively. PrE formation depends on Nanog by a non-cell-autonomous mechanism. To decipher early cell- and non-cell-autonomous effects, we performed a mosaic knockdown of Nanog and found that this is sufficient to induce a PrE fate cell autonomously. Strikingly, in Nanog null embryos, Gata6 expression is maintained, showing that initiation of the PrE program is Nanog independent. Treatment of Nanog null embryos with pharmacological inhibitors revealed tha... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513813 Tue, 13 Dec 2011 05:00:00 +0100 5513813 http://www.medworm.com/index.php?rid=5513812&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172670%26dopt%3DAbstract Authors: Tang W, Zhang Y, Xu W, Harden TK, Sondek J, Sun L, Li L, Wu D Abstract Neutrophils, in response to a chemoattractant gradient, undergo dynamic F-actin remodeling, a process important for their directional migration or chemotaxis. However, signaling mechanisms for chemoattractants to regulate the process are incompletely understood. Here, we characterized chemoattractant-activated signaling mechanisms that regulate cofilin dephosphorylation and actin cytoskeleton reorganization and are critical for neutrophil polarization and chemotaxis. In neutrophils, chemoattractants induced phosphorylation and inhibition of GSK3 via both PLCβ-PKC and PI3Kγ-AKT pathways, leading to the attenuation of GSK3-mediated phosphorylation and inhibition of the cofilin phosphatase slingshot2 an... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513812 Tue, 13 Dec 2011 05:00:00 +0100 5513812 http://www.medworm.com/index.php?rid=5513811&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172671%26dopt%3DAbstract Authors: Campbell K, Whissell G, Franch-Marro X, Batlle E, Casanova J Abstract The epithelial-to-mesenchymal transition (EMT) converts cells from static epithelial to migratory mesenchymal states (Hay, 1995). Here, we demonstrate that EMT in the Drosophila endoderm is dependent on the GATA-factor Serpent (Srp), and that Srp acts as a potent trigger for this transition when activated ectopically. We show that Srp affects endodermal-EMT through a downregulation of junctional dE-Cadherin (dE-Cad) protein, without a block in its transcription. Moreover, the relocalization of dE-Cad is achieved through the direct repression of crumbs (crb) by Srp. Finally, we show that hGATA-6, an ortholog of Srp, induces a similar transition in mammalian cells. Similar to Srp, hGATA-6 acts through the ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513811 Tue, 13 Dec 2011 05:00:00 +0100 5513811 http://www.medworm.com/index.php?rid=5513810&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172672%26dopt%3DAbstract Authors: Dombecki CR, Chiang AC, Kang HJ, Bilgir C, Stefanski NA, Neva BJ, Klerkx EP, Nabeshima K Abstract Homologous chromosome pairing is a prerequisite to establish physical linkage between homologs, which is critical for faithful chromosome segregation during meiosis I. The establishment of pairing is genetically separable from subsequent synapsis, defined as stabilization of pairing by the synaptonemal complex (SC). The underlying mechanism of presynaptic pairing is poorly understood. In the nematode Caenorhabditis elegans, a unique cis-acting element, the pairing center (PC), is essential for presynaptic pairing; however, it is not known whether and how the remainder of the chromosome contributes to presynaptic pairing. Here we report direct evidence for presynaptic pairing a... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513810 Tue, 13 Dec 2011 05:00:00 +0100 5513810 http://www.medworm.com/index.php?rid=5513809&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172673%26dopt%3DAbstract Authors: Su KC, Takaki T, Petronczki M Abstract In animal cells, formation of the cytokinetic furrow requires activation of the GTPase RhoA by the guanine nucleotide exchange factor Ect2. How Ect2, which is associated with the spindle midzone, controls RhoA activity at the equatorial cortex during anaphase is not understood. Here, we show that Ect2 concentrates at the equatorial membrane during cytokinesis in live cells. Ect2 membrane association requires a pleckstrin homology domain and a polybasic cluster that bind to phosphoinositide lipids. Both guanine nucleotide exchange function and membrane targeting of Ect2 are essential for RhoA activation and cleavage furrow formation in human cells. Membrane localization of Ect2 is spatially confined to the equator by centralspindlin, E... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513809 Tue, 13 Dec 2011 05:00:00 +0100 5513809 http://www.medworm.com/index.php?rid=5513808&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172674%26dopt%3DAbstract In this study, we highlight a function of six Arabidopsis MATH-BTB proteins in ABA signaling. MATH-BTB proteins act as substrate-binding adaptors for the Cullin3-based ubiquitin E3 ligase. Our genetic and biochemical experiments demonstrate that the MATH-BTB proteins directly interact with and target for proteasomal degradation the class I homeobox-leucine zipper (HD-ZIP) transcription factor ATHB6, which was previously identified as a negative regulator of ABA responses. Reducing CUL3(BPM) function leads to higher ATHB6 protein accumulation, reducing plant growth and fertility, and affects stomatal behavior and responses to ABA. We further demonstrate that ABA negatively regulates ATHB6 protein turnover, a situation reminiscent to ABI5, another transcription factor involved in ABA signali... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513808 Tue, 13 Dec 2011 05:00:00 +0100 5513808 http://www.medworm.com/index.php?rid=5513807&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172675%26dopt%3DAbstract Authors: Vatén A, Dettmer J, Wu S, Stierhof YD, Miyashima S, Yadav SR, Roberts CJ, Campilho A, Bulone V, Lichtenberger R, Lehesranta S, Mähönen AP, Kim JY, Jokitalo E, Sauer N, Scheres B, Nakajima K, Carlsbecker A, Gallagher KL, Helariutta Y Abstract Plant cells are connected through plasmodesmata (PD), membrane-lined channels that allow symplastic movement of molecules between cells. However, little is known about the role of PD-mediated signaling during plant morphogenesis. Here, we describe an Arabidopsis gene, CALS3/GSL12. Gain-of-function mutations in CALS3 result in increased accumulation of callose (β-1,3-glucan) at the PD, a decrease in PD aperture, defects in root development, and reduced intercellular trafficking. Enhancement of CALS3 expression during phloem developm... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513807 Tue, 13 Dec 2011 05:00:00 +0100 5513807 http://www.medworm.com/index.php?rid=5513806&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172676%26dopt%3DAbstract Authors: Jin Y, Sultana A, Gandhi P, Franklin E, Hamamoto S, Khan AR, Munson M, Schekman R, Weisman LS Abstract Vesicle transport requires four steps: vesicle formation, movement, tethering, and fusion. In yeast, two Rab GTPases, Ypt31/32, are required for post-Golgi vesicle formation. A third Rab GTPase, Sec4, and the exocyst act in tethering and fusion of these vesicles. Vesicle production is coupled to transport via direct interaction between Ypt31/32 and the yeast myosin V, Myo2. Here we show that Myo2 interacts directly with Sec4 and the exocyst subunit Sec15. Disruption of these interactions results in compromised growth and the accumulation of secretory vesicles. We identified the Sec15-binding region on Myo2 and also identified residues on Sec15 required for interaction wit... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513806 Tue, 13 Dec 2011 05:00:00 +0100 5513806 http://www.medworm.com/index.php?rid=5513805&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172677%26dopt%3DAbstract Authors: Rosa-Ferreira C, Munro S Abstract Lysosomes move bidirectionally on microtubules, and this motility can be stimulated by overexpression of the small GTPase Arl8. By using affinity chromatography, we find that Arl8-GTP binds to the soluble protein SKIP (SifA and kinesin-interacting protein, aka PLEKHM2). SKIP was originally identified as a target of the Salmonella effector protein SifA and found to bind the light chain of kinesin-1 to activate the motor on the bacteria's replicative vacuole. We show that in uninfected cells both Arl8 and SKIP are required for lysosomes to distribute away from the microtubule-organizing center. We identify two kinesin light chain binding motifs in SKIP that are required for lysosomes to accumulate kinesin-1 and redistribute to the cell peri... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513805 Tue, 13 Dec 2011 05:00:00 +0100 5513805 http://www.medworm.com/index.php?rid=5513804&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172678%26dopt%3DAbstract Authors: Thummel CS Abstract Genetic studies of Drosophila eye imaginal disc development have provided a classic approach to dissect the coordination of cell proliferation and differentiation. This paper describes the characterization of a mutation in the tenured gene, which was recovered from a large-scale genetic screen based on its glossy eye phenotype. The authors show that this phenotype arises from a specific block in the G1 phase of the cell cycle, with no apparent effects on cell viability or differentiation. The remarkable part of this paper lies in the discovery that tenured encodes a subunit of cytochrome c oxidase, a key component in the electron transport chain. The authors show that the reduced ATP levels in tenured mutant cells leads to activation of the energy sens... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513804 Tue, 13 Dec 2011 05:00:00 +0100 5513804 http://www.medworm.com/index.php?rid=5513803&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172679%26dopt%3DAbstract Authors: Wagner EF Abstract I very much enjoyed reading a Developmental Cell paper from Freddy Radtke's laboratory describing exciting findings regarding the requirement of Notch1 signaling for maintenance of corneal integrity during wound repair. The authors showed that Notch1 controls corneal cell fate and prevents keratinization and tissue differentiation into a skin-like epithelium, which is causal to corneal blindness. They further demonstrated that this effect is through negative control of FGF-2 and vascularization and through positive control of vitamin A metabolism. These results provided novel insights into the role of Notch1 as a master regulator of corneal cell fate to prevent skin-like epithelium formation upon injury. I consider these findings particularly interesting... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513803 Tue, 13 Dec 2011 05:00:00 +0100 5513803 http://www.medworm.com/index.php?rid=5513820&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169070%26dopt%3DAbstract Authors: Silva MC, Bodor DL, Stellfox ME, Martins NM, Hochegger H, Foltz DR, Jansen LE Abstract Centromeres form the site of chromosome attachment to microtubules during mitosis. Identity of these loci is maintained epigenetically by nucleosomes containing the histone H3 variant CENP-A. Propagation of CENP-A chromatin is uncoupled from DNA replication initiating only during mitotic exit. We now demonstrate that inhibition of Cdk1 and Cdk2 activities is sufficient to trigger CENP-A assembly throughout the cell cycle in a manner dependent on the canonical CENP-A assembly machinery. We further show that the key CENP-A assembly factor Mis18BP1(HsKNL2) is phosphorylated in a cell cycle-dependent manner that controls its centromere localization during mitotic exit. These results strongly... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513820 Tue, 06 Dec 2011 05:00:00 +0100 5513820 http://www.medworm.com/index.php?rid=5513819&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169071%26dopt%3DAbstract Authors: Weber GF, Bjerke MA, Desimone DW Abstract Collective cell migration requires maintenance of adhesive contacts between adjacent cells, coordination of polarized cell protrusions, and generation of propulsive traction forces. We demonstrate that mechanical force applied locally to C-cadherins on single Xenopus mesendoderm cells is sufficient to induce polarized cell protrusion and persistent migration typical of individual cells within a collectively migrating tissue. Local tension on cadherin adhesions induces reorganization of the keratin intermediate filament network toward these stressed sites. Plakoglobin, a member of the catenin family, is localized to cadherin adhesions under tension and is required for both mechanoresponsive cell behavior and assembly of the keratin ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5513819 Tue, 06 Dec 2011 05:00:00 +0100 5513819 http://www.medworm.com/index.php?rid=5493905&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137762%26dopt%3DAbstract Authors: Lindeman LC, Andersen IS, Reiner AH, Li N, Aanes H, Ostrup O, Winata C, Mathavan S, Müller F, Aleström P, Collas P Abstract A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA, we demonstrate here an epigenetic prepatterning of de... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5493905 Wed, 30 Nov 2011 05:00:00 +0100 5493905 http://www.medworm.com/index.php?rid=5493904&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137763%26dopt%3DAbstract Authors: Tu Z, Aird KM, Bitler BG, Nicodemus JP, Beeharry N, Xia B, Yen TJ, Zhang R Abstract Here, we report a cell-intrinsic mechanism by which oncogenic RAS promotes senescence while predisposing cells to senescence bypass by allowing for secondary hits. We show that oncogenic RAS inactivates the BRCA1 DNA repair complex by dissociating BRCA1 from chromatin. This event precedes senescence-associated cell cycle exit and coincides with the accumulation of DNA damage. Downregulation of BRIP1, a physiological partner of BRCA1 in the DNA repair pathway, triggers BRCA1 chromatin dissociation. Conversely, ectopic BRIP1 rescues BRCA1 chromatin dissociation and suppresses RAS-induced senescence and the DNA damage response. Significantly, cells undergoing senescence do not exhibit a BRCA1... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5493904 Wed, 30 Nov 2011 05:00:00 +0100 5493904 http://www.medworm.com/index.php?rid=5493907&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118769%26dopt%3DAbstract Authors: Carmona-Fontaine C, Theveneau E, Tzekou A, Tada M, Woods M, Page KM, Parsons M, Lambris JD, Mayor R Abstract Collective cell migration is a mode of movement crucial for morphogenesis and cancer metastasis. However, little is known about how migratory cells coordinate collectively. Here we show that mutual cell-cell attraction (named here coattraction) is required to maintain cohesive clusters of migrating mesenchymal cells. Coattraction can counterbalance the natural tendency of cells to disperse via mechanisms such as contact inhibition and epithelial-to-mesenchymal transition. Neural crest cells are coattracted via the complement fragment C3a and its receptor C3aR, revealing an unexpected role of complement proteins in early vertebrate development. Loss of coattraction d... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5493907 Wed, 23 Nov 2011 05:00:00 +0100 5493907 http://www.medworm.com/index.php?rid=5493906&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118770%26dopt%3DAbstract We report a critical role for SAG in controlling vascular and neural development by modulating RAS activity via promoting degradation of neurofibromatosis type 1 (NF1). Mice mutant for Sag died at embryonic day 11.5-12.5 with severe abnormalities in vascular and nervous system. Sag inactivation caused Nf1 accumulation and Ras inhibition, which blocks embryonic stem (ES) cells from undergoing endothelial differentiation and inhibits angiogenesis and proliferation in teratomas. Simultaneous Nf1 deletion fully rescues the differentiation defects in Sag(-/-) ES cells and partially rescues vascular and neural defects in Sag(-/-) embryos, suggesting that the effects of Sag deletion may not be solely explained by Nf1 misregulation. Collectively, our study identifies NF1 as a physiological subst... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5493906 Tue, 22 Nov 2011 05:00:00 +0100 5493906 http://www.medworm.com/index.php?rid=5493908&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100263%26dopt%3DAbstract Authors: Kagermeier-Schenk B, Wehner D, Ozhan-Kizil G, Yamamoto H, Li J, Kirchner K, Hoffmann C, Stern P, Kikuchi A, Schambony A, Weidinger G Abstract Wnt proteins can activate distinct signaling pathways, but little is known about the mechanisms regulating pathway selection. Here we show that the metastasis-associated transmembrane protein Wnt-activated inhibitory factor 1 (Waif1/5T4) interferes with Wnt/β-catenin signaling and concomitantly activates noncanonical Wnt pathways. Waif1 inhibits β-catenin signaling in zebrafish and Xenopus embryos as well as in mammalian cells, and zebrafish waif1a acts as a direct feedback inhibitor of wnt8-mediated mesoderm and neuroectoderm patterning during zebrafish gastrulation. Waif1a binds to the Wnt coreceptor LRP6 and inhibits Wnt-induced... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5493908 Thu, 17 Nov 2011 05:00:00 +0100 5493908 http://www.medworm.com/index.php?rid=5493909&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100262%26dopt%3DAbstract Authors: Daikoku T, Cha J, Sun X, Tranguch S, Xie H, Fujita T, Hirota Y, Lydon J, Demayo F, Maxson R, Dey SK Abstract An effective bidirectional communication between an implantation-competent blastocyst and the receptive uterus is a prerequisite for mammalian reproduction. The blastocyst will implant only when this molecular cross-talk is established. Here we show that the muscle segment homeobox gene (Msh) family members Msx1 and Msx2, which are two highly conserved genes critical for epithelial-mesenchymal interactions during development, also play crucial roles in embryo implantation. Loss of Msx1/Msx2 expression correlates with altered uterine luminal epithelial cell polarity and affects E-cadherin/β-catenin complex formation through the control of Wnt5a expression. Applicati... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5493909 Wed, 16 Nov 2011 05:00:00 +0100 5493909 http://www.medworm.com/index.php?rid=5421769&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055343%26dopt%3DAbstract Authors: Jukam D, Desplan C Abstract Patterning the Drosophila retina for color vision relies on postmitotic specification of photoreceptor subtypes. R8 photoreceptors express one of two light-sensing Rhodopsins, Rh5 or Rh6. This fate decision involves a bistable feedback loop between Melted, a PH-domain protein, and Warts, a kinase in the Hippo growth pathway. Here, we show that a subset of the Hippo pathway-Merlin, Kibra, and Lethal(2)giant larvae (Lgl), but not Expanded or Fat-is required for Warts expression and activity in R8 to specify Rh6 fate. Melted represses warts transcription to disrupt Hippo pathway activity and specify Rh5 fate. Therefore, R8 Hippo signaling exhibits ON-or-OFF regulation, promoting mutually exclusive fates. Furthermore, Merlin and Lgl are continuously... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421769 Tue, 15 Nov 2011 05:00:00 +0100 5421769 http://www.medworm.com/index.php?rid=5421768&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055344%26dopt%3DAbstract Authors: Deselm CJ, Miller BC, Zou W, Beatty WL, van Meel H, Takahata Y, Klumperman J, Tooze SA, Teitelbaum SL, Virgin HW Abstract Osteoclasts resorb bone via the ruffled border, whose complex folds are generated by secretory lysosome fusion with bone-apposed plasma membrane. Lysosomal fusion with the plasmalemma results in acidification of the resorptive microenvironment and release of CatK to digest the organic matrix of bone. The means by which secretory lysosomes are directed to fuse with the ruffled border are enigmatic. We show that proteins essential for autophagy, including Atg5, Atg7, Atg4B, and LC3, are important for generating the osteoclast ruffled border, the secretory function of osteoclasts, and bone resorption in vitro and in vivo. Further, Rab7, which is required... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421768 Tue, 15 Nov 2011 05:00:00 +0100 5421768 http://www.medworm.com/index.php?rid=5421767&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075141%26dopt%3DAbstract Authors: Jaspersen SL, Hawley RS Abstract In C. elegans, meiotic chromosome pairing is initiated by association of chromosomal sites known as pairing centers (PCs) with the nuclear periphery. The Dernburg and Zetka laboratories have shown that recruitment of Polo kinases to PCs at the nuclear envelope is essential to promote PC complex aggregation, pairing, and synapsis. PMID: 22075141 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421767 Tue, 15 Nov 2011 05:00:00 +0100 5421767 http://www.medworm.com/index.php?rid=5421766&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075142%26dopt%3DAbstract Authors: Follmer NE, Francis NJ Abstract During mitosis, most transcription ceases. Mitotic gene bookmarking marks genes for reactivation to ensure reestablishment of transcription states and cell-cycle progression. In a recent issue of Nature Cell Biology, Zhao et al. (2011) investigate how gene bookmarking leads to accelerated kinetics of transcriptional reactivation after mitosis. PMID: 22075142 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421766 Tue, 15 Nov 2011 05:00:00 +0100 5421766 http://www.medworm.com/index.php?rid=5421765&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075143%26dopt%3DAbstract Authors: Gelman A, Elazar Z Abstract Autophagy is an intracellular membrane-trafficking pathway for the delivery of proteins and organelles to lysosomes for degradation and recycling. DeSelm and coworkers (2011) now describe an essential role for autophagic proteins in the trafficking and fusion of lysosomes at the site of bone resorption: the osteoclast ruffled border. PMID: 22075143 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421765 Tue, 15 Nov 2011 05:00:00 +0100 5421765 http://www.medworm.com/index.php?rid=5421749&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075144%26dopt%3DAbstract Authors: Bankaitis VA, Grabon A Abstract Kim et al. (2011) challenge the dogma that phosphatidylinositol synthesis is restricted to the endoplasmic reticulum (ER) by showing that a mobile membrane compartment transports phosphatidylinositol synthase from the ER to numerous cellular compartments, including the plasma membrane. These findings significantly impact our view of phosphoinositide signaling in the cell. PMID: 22075144 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421749 Tue, 15 Nov 2011 05:00:00 +0100 5421749 http://www.medworm.com/index.php?rid=5421748&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075145%26dopt%3DAbstract Authors: Kim YJ, Guzman-Hernandez ML, Balla T Abstract Polyphosphoinositides are lipid signaling molecules generated from phosphatidylinositol (PtdIns) with critical roles in vesicular trafficking and signaling. It is poorly understood where PtdIns is located within cells and how it moves around between membranes. Here we identify a hitherto-unrecognized highly mobile membrane compartment as the site of PtdIns synthesis and a likely source of PtdIns of all membranes. We show that the PtdIns-synthesizing enzyme PIS associates with a rapidly moving compartment of ER origin that makes ample contacts with other membranes. In contrast, CDP-diacylglycerol synthases that provide PIS with its substrate reside in the tubular ER. Expression of a PtdIns-specific bacterial PLC generates diacyl... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421748 Tue, 15 Nov 2011 05:00:00 +0100 5421748 http://www.medworm.com/index.php?rid=5421742&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075146%26dopt%3DAbstract Authors: Wang H, Yang C, Zhang C, Wang N, Lu D, Wang J, Zhang S, Wang ZX, Ma H, Wang X Abstract The plasma membrane-localized plant steroid hormone receptor, BRASSINOSTEROID INSENSITIVE 1 (BRI1), is quiescent in the absence of steroids, largely due to a negative regulator, BRI1 KINASE INHIBITOR 1 (BKI1). Here, we report that the steroid-induced, plasma membrane-dissociated and phosphorylated BKI1 also plays positive roles in BR signaling by interacting with a subset of 14-3-3 proteins. The cytosolic fraction of BKI1 carboxyl terminal region enhances BR signaling. Mutations of two serine residues in this region lead to reduced phosphorylation by the BRI1 kinase and constitutive plasma membrane localization. The 14-3-3 proteins can interact with the phosphorylated BKI1 through a moti... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421742 Tue, 15 Nov 2011 05:00:00 +0100 5421742 http://www.medworm.com/index.php?rid=5421734&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075147%26dopt%3DAbstract Authors: Boggiano JC, Vanderzalm PJ, Fehon RG Abstract Recent studies have shown that the Hippo-Salvador-Warts (HSW) pathway restrains tissue growth by phosphorylating and inactivating the oncoprotein Yorkie. How growth-suppressive signals are transduced upstream of Hippo remains unclear. We show that the Sterile 20 family kinase, Tao-1, directly phosphorylates T195 in the Hippo activation loop and that, like other HSW pathway genes, Tao-1 functions to restrict cell proliferation in developing imaginal epithelia. This relationship appears to be evolutionarily conserved, because mammalian Tao-1 similarly affects MST kinases. In S2 cells, Tao-1 mediates the effects of the upstream HSW components Merlin and Expanded, consistent with the idea that Tao-1 functions in tissues to regulate... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421734 Tue, 15 Nov 2011 05:00:00 +0100 5421734 http://www.medworm.com/index.php?rid=5421733&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075148%26dopt%3DAbstract Authors: Poon CL, Lin JI, Zhang X, Harvey KF Abstract The Salvador-Warts-Hippo (SWH) pathway is a complex signaling network that controls both developmental and regenerative tissue growth. Using a genetic screen in Drosophila melanogaster, we identified the sterile 20-like kinase, Tao-1, as an SWH pathway member. Tao-1 controls various biological phenomena, including microtubule dynamics, animal behavior, and brain development. Here we describe a role for Tao-1 as a regulator of epithelial tissue growth that modulates activity of the core SWH pathway kinase cassette. Tao-1 functions together with Hippo to activate Warts-mediated repression of Yorkie. Tao-1's ability to control SWH pathway activity is evolutionarily conserved because human TAO1 can suppress activity of the Yorkie or... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421733 Tue, 15 Nov 2011 05:00:00 +0100 5421733 http://www.medworm.com/index.php?rid=5421732&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075149%26dopt%3DAbstract We report tissue-specific mouse mutant analyses identifying the bone morphogenetic protein (BMP) pathway as a key regulator of ventral morphogenesis. BMP2 expressed in anterior visceral endoderm (AVE) signals to epiblast derivatives during gastrulation to orchestrate initial stages of ventral morphogenesis, including foregut development and positioning of head and heart. These findings identify unanticipated functions for the AVE in organizing the gastrulating embryo and indicate that visceral endoderm-expressed BMP2 coordinates morphogenetic cell behaviors in multiple epiblast lineages. VIDEO ABSTRACT: PMID: 22075149 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421732 Tue, 15 Nov 2011 05:00:00 +0100 5421732 http://www.medworm.com/index.php?rid=5421730&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075150%26dopt%3DAbstract Authors: Gandhi SR, Gierliński M, Mino A, Tanaka K, Kitamura E, Clayton L, Tanaka TU Abstract How kinetochores regulate microtubule dynamics to ensure proper kinetochore-microtubule interactions is unknown. Here, we studied this during early mitosis in Saccharomyces cerevisiae. When a microtubule shrinks and its plus end reaches a kinetochore bound to its lateral surface, the microtubule end attempts to tether the kinetochore. This process often fails and, responding to this failure, microtubule rescue (conversion from shrinkage to growth) occurs, preventing kinetochore detachment from the microtubule end. This rescue is promoted by Stu2 transfer (ortholog of vertebrate XMAP215/ch-TOG) from the kinetochore to the microtubule end. Meanwhile, microtubule rescue distal to the kinetoc... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421730 Tue, 15 Nov 2011 05:00:00 +0100 5421730 http://www.medworm.com/index.php?rid=5421721&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075151%26dopt%3DAbstract Authors: Brugge J Abstract Prior to the publication of this report, the importance of endocytotic and exocytotic recycling of integrins was just beginning to be recognized. However, the findings in this report provided significant new insights into the mechanisms mediating integrin recycling and the critical importance of spatially regulated recycling in controlling specific aspects of cell migration and invasion. The Rab family GTPase RAB25, which has been implicated in tumor progression, was found to bind directly to β1 integrin and, through this interaction, specifically deliver α5β1-containing vesicles to the tips of pseudopodial extensions. This RAB25-integrin interaction was found to be critical for directional invasion of tumor cells in 3D extracellular matrix environment... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421721 Tue, 15 Nov 2011 05:00:00 +0100 5421721 http://www.medworm.com/index.php?rid=5421718&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22075152%26dopt%3DAbstract Authors: Krämer H Abstract The paper by Kobayashi et al. triggered fond memories and curious questions, as one might expect when meeting a couple of old, almost forgotten friends. As a post doc in Larry Zipursky's laboratory, I worked in a team trying to understand how Boss/Sevenless signaling directs the presence of one and only one R7 cell in each ommatidium of the fly eye. Almost 20 years later, an odd sense of ownership contributed to my first knee-jerk reaction to the title of the paper claiming a role for Boss and Sevenless in early male gonads: Those mutants are fertile! How, then, could either Boss or Sevenless be important for the niche in which male germline stem cells reside? But, thinking back, neither boss nor sevenless mutants are blind, and yet they told us a lot a... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5421718 Tue, 15 Nov 2011 05:00:00 +0100 5421718 http://www.medworm.com/index.php?rid=5380164&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22033112%26dopt%3DAbstract Authors: Shi J, Luo L, Eash J, Ibebunjo C, Glass DJ Abstract Insulin-like growth factor 1 (IGF1) induces skeletal muscle hypertrophy by activating the IGF1R/IRS1/PI3K/Akt pathway. However the effect of IGF1 in differentiated muscle is limited by IRS1 ubiquitination and proteasome-mediated breakdown. In skeletal muscle, IGF1R activation sensitizes IRS1 to degradation, and a screen for the responsible E3 ligase identified Fbxo40 as mediating this rapid turnover of IRS1, since IRS1 loss can be rescued by knockdown of Fbxo40. In biochemical assays, an SCF E3 ligase complex containing Fbxo40 directly ubiquitinates IRS1, and this activity is enhanced by increased tyrosine phosphorylation of IRS1. Fbxo40 is muscle specific in expression and is upregulated during differentiation. Knockdown... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5380164 Tue, 25 Oct 2011 04:00:00 +0100 5380164 http://www.medworm.com/index.php?rid=5380163&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22036506%26dopt%3DAbstract We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP-bound Rac1 and catalyzes its polyubiquitylation. HACE1 expression increases the ubiquitylation of Rac1, when the GTPase is activated by point mutations or by the GEF-domain of Dbl. RNAi-mediated depletion of HACE1 blocks the ubiquitylation of active Rac1 and increases GTP-bound Rac1 cellular levels. HACE1 antagonizes cell isotropic spreading, a hallmark of Rac1 activation, and is required for endothelial cell monolayer invasion by bacteria. Together, these data establish the role of the HACE1 E3 ubiquitin-ligase in controlling Rac1 ubiquitylation and activity. PMID: 22036506 [PubMed - as supplied by publisher] (Source:... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5380163 Tue, 25 Oct 2011 04:00:00 +0100 5380163 http://www.medworm.com/index.php?rid=5380165&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018922%26dopt%3DAbstract Authors: Harper NC, Rillo R, Jover-Gil S, Assaf ZJ, Bhalla N, Dernburg AF Abstract Faithful segregation of homologous chromosomes during meiosis requires pairing, synapsis, and crossing-over. In C. elegans, homolog pairing and synapsis depend on pairing centers (PCs), special regions near one end of each chromosome that interact with the nuclear envelope (NE) and cytoplasmic microtubules. Here, we report that PCs are required for nuclear reorganization at the onset of meiosis. We demonstrate that PCs recruit the Polo-like kinase PLK-2 to induce NE remodeling, chromosome pairing, and synapsis. Recruitment of PLK-2 is also required to mediate a cell cycle delay and selective apoptosis of nuclei containing unsynapsed chromosomes, establishing a molecular link between these two qualit... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5380165 Wed, 19 Oct 2011 04:00:00 +0100 5380165 http://www.medworm.com/index.php?rid=5380166&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018921%26dopt%3DAbstract We report that the polo kinases PLK-1 and PLK-2 are targeted to the PC by ZIM/HIM-8-pairing proteins. Loss of plk-2 inhibits chromosome pairing and licenses synapsis between nonhomologous chromosomes, indicating that PLK-2 is required for PC-mediated interhomolog interactions. plk-2 is also required for meiosis-specific phosphorylation of SUN-1 and establishment of dynamic SUN/KASH (SUN-1/ZYG-12) modules that promote homolog pairing. Our results provide key insights into the regulation of homolog pairing and reveal that targeting of polo-like kinases to the NE by meiotic chromosomes establishes the conserved linkages to cytoskeletal forces needed for homology assessment. PMID: 22018921 [PubMed - as supplied by publisher] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5380166 Tue, 18 Oct 2011 04:00:00 +0100 5380166 http://www.medworm.com/index.php?rid=5345933&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014515%26dopt%3DAbstract Authors: Herrmann JM Abstract Cristae junctions mark the boundaries of respiratory compartments in the inner mitochondrial membrane. In this issue of Developmental Cell, von der Malsburg et al. (2011) identify a complex, MINOS, that organizes cristae junctions. Mitofilin/Fcj1, the central component of the MINOS complex, also connects the inner membrane to outer membrane protein import machinery. PMID: 22014515 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345933 Tue, 18 Oct 2011 04:00:00 +0100 5345933 http://www.medworm.com/index.php?rid=5345932&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014516%26dopt%3DAbstract Authors: Ghose A, Shashidhara LS Abstract In this issue of Developmental Cell, Odajima, Wills, and colleagues (2011) demonstrate that the cell-cycle regulator, cyclin E, sequesters Cdk5, a key regulator of neuronal development and synaptic plasticity. This cell-cycle-independent function of cyclin E reveals an exciting mode of Cdk5 regulation in postmitotic neurons and offers a window into evolutionary parsimony. PMID: 22014516 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345932 Tue, 18 Oct 2011 04:00:00 +0100 5345932 http://www.medworm.com/index.php?rid=5345931&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014517%26dopt%3DAbstract Authors: Cariboni A, Ruhrberg C Abstract Neurovascular integration during embryonic development is essential for adult physiology. In this issue of Developmental Cell, Gutnick et al. (2011) report that hypothalamic neurons secrete oxytocin as a guidance cue for endothelial cells to establish their vascular supply-a prerequisite for neuroendocrine secretion from the neurohyophysis in adult life. PMID: 22014517 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345931 Tue, 18 Oct 2011 04:00:00 +0100 5345931 http://www.medworm.com/index.php?rid=5345930&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014518%26dopt%3DAbstract Authors: Lizunov V, Chlanda P, Kraft M, Zimmerberg J Abstract The mechanistic basis of how cells respond to increased fatty acids (FAs) is murky but potentially involves receptor-mediated activation or inhibition by different FA classes. Holzer et al. (2011) recently propose in Cell that expansion of intracellular membrane microdomains induced by saturated FA recruit and activate c-Src for JNK activation. PMID: 22014518 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345930 Tue, 18 Oct 2011 04:00:00 +0100 5345930 http://www.medworm.com/index.php?rid=5345929&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014519%26dopt%3DAbstract Authors: Ladher RK Abstract The earliest steps in tooth development depend on signaling interactions that result in the condensation of mandibular mesenchyme into the tooth bud. Reporting in this issue of Developmental Cell,Mammoto et al. (2011) find that chemotactic signals coordinate condensation and that the compressive force generated is sufficient to induce tooth bud gene expression. PMID: 22014519 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345929 Tue, 18 Oct 2011 04:00:00 +0100 5345929 http://www.medworm.com/index.php?rid=5345928&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014520%26dopt%3DAbstract Authors: Stepanova AN, Alonso JM Abstract In this issue of Developmental Cell, Marhavý et al. (2011) uncover a transcription-independent molecular mechanism of interaction between auxin and cytokinin in the regulation of plant meristem function. By modulating endocytic trafficking of PIN1, cytokinin controls auxin flux and, therefore, auxin gradients. PMID: 22014520 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345928 Tue, 18 Oct 2011 04:00:00 +0100 5345928 http://www.medworm.com/index.php?rid=5345927&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014521%26dopt%3DAbstract Authors: Biggin MD Abstract To understand how transcription factors function, it is essential to determine the range of genes that they each bind and regulate in vivo. Here I review evidence that most animal transcription factors each bind to a majority of genes over a quantitative series of DNA occupancy levels. These continua span functional, quasifunctional, and nonfunctional DNA binding events. Factor regulatory specificities are distinguished by quantitative differences in DNA occupancy patterns. I contrast these results with models for transcription networks that define discrete sets of direct target and nontarget genes and consequently do not fully capture the complexity observed in vivo. PMID: 22014521 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345927 Tue, 18 Oct 2011 04:00:00 +0100 5345927 http://www.medworm.com/index.php?rid=5345926&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014522%26dopt%3DAbstract We present a unique example of axons affecting endothelial morphogenesis through secretion of a neuropeptide. PMID: 22014522 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345926 Tue, 18 Oct 2011 04:00:00 +0100 5345926 http://www.medworm.com/index.php?rid=5345925&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014523%26dopt%3DAbstract Authors: Seetharaman A, Selman G, Puckrin R, Barbier L, Wong E, D'Souza SA, Roy PJ Abstract The netrins and slits are two families of widely conserved cues that guide axons and cells along the dorsal-ventral (D-V) axis of animals. These cues typically emanate from the dorsal or ventral midlines and provide spatial information to migrating cells by forming gradients along the D-V axis. Some cell types, however, extend processes to both the dorsal and ventral midlines, suggesting the existence of additional guidance cues that are secreted from both midlines. Here, we report that a previously uncharacterized protein called MADD-4 is secreted by the dorsal and ventral nerve cords of the nematode C. elegans to attract sensory axons and muscle membrane extensions called muscle arms. M... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345925 Tue, 18 Oct 2011 04:00:00 +0100 5345925 http://www.medworm.com/index.php?rid=5345924&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014524%26dopt%3DAbstract Authors: Deng Q, Yoo SK, Cavnar PJ, Green JM, Huttenlocher A Abstract Neutrophil homeostasis is essential for host defense. Here we identify dual roles for Rac2 during neutrophil homeostasis using a zebrafish model of primary immune deficiency induced by the human inhibitory Rac2D57N mutation in neutrophils. Noninvasive live imaging of Rac2 morphants or Rac2D57N zebrafish larvae demonstrates an essential role for Rac2 in regulating 3D motility and the polarization of F-actin dynamics and PI(3)K signaling in vivo. Tracking of photolabeled Rac2-deficient neutrophils from hematopoietic tissue also shows increased mobilization into the circulation, indicating that neutrophil mobilization does not require traditionally defined cell motility. Moreover, excessive neutrophil retention in ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345924 Tue, 18 Oct 2011 04:00:00 +0100 5345924 http://www.medworm.com/index.php?rid=5345923&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014525%26dopt%3DAbstract Authors: Lee Y, Fryer JD, Kang H, Crespo-Barreto J, Bowman AB, Gao Y, Kahle JJ, Hong JS, Kheradmand F, Orr HT, Finegold MJ, Zoghbi HY Abstract Although expansion of CAG repeats in ATAXIN1 (ATXN1) causes Spinocerebellar ataxia type 1, the functions of ATXN1 and ATAXIN1-Like (ATXN1L) remain poorly understood. To investigate the function of these proteins, we generated and characterized Atxn1L(-/-) and Atxn1(-/-); Atxn1L(-/-) mice. Atxn1L(-/-) mice have hydrocephalus, omphalocele, and lung alveolarization defects. These phenotypes are more penetrant and severe in Atxn1(-/-); Atxn1L(-/-) mice, suggesting that ATXN1 and ATXN1L are functionally redundant. Upon pursuing the molecular mechanism, we discovered that several Matrix metalloproteinase (Mmp) genes are overexpressed and that the... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345923 Tue, 18 Oct 2011 04:00:00 +0100 5345923 http://www.medworm.com/index.php?rid=5345922&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014526%26dopt%3DAbstract Authors: Iyer-Pascuzzi AS, Jackson T, Cui H, Petricka JJ, Busch W, Tsukagoshi H, Benfey PN Abstract Stress responses in plants are tightly coordinated with developmental processes, but interaction of these pathways is poorly understood. We used genome-wide assays at high spatiotemporal resolution to understand the processes that link development and stress in the Arabidopsis root. Our meta-analysis finds little evidence for a universal stress response. However, common stress responses appear to exist with many showing cell type specificity. Common stress responses may be mediated by cell identity regulators because mutations in these genes resulted in altered responses to stress. Evidence for a direct role for cell identity regulators came from genome-wide binding profiling of the ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345922 Tue, 18 Oct 2011 04:00:00 +0100 5345922 http://www.medworm.com/index.php?rid=5345921&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014527%26dopt%3DAbstract Authors: Vrailas-Mortimer A, Del Rivero T, Mukherjee S, Nag S, Gaitanidis A, Kadas D, Consoulas C, Duttaroy A, Sanyal S Abstract Molecular mechanisms that concordantly regulate stress, life span, and aging remain incompletely understood. Here, we demonstrate that in Drosophila, a p38 MAP kinase (p38K)/Mef2/MnSOD pathway is a coregulator of stress and life span. Hence, overexpression of p38K extends life span in a MnSOD-dependent manner, whereas inhibition of p38K causes early lethality and precipitates age-related motor dysfunction and stress sensitivity, that is rescued through muscle-restricted (but not neuronal) add-back of p38K. Additionally, mutations in p38K are associated with increased protein carbonylation and Nrf2-dependent transcription, while adversely affecting metabol... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345921 Tue, 18 Oct 2011 04:00:00 +0100 5345921 http://www.medworm.com/index.php?rid=5345920&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014528%26dopt%3DAbstract Authors: Perrimon N Abstract Large-scale studies in various model systems including Drosophila, fish, and the mouse have documented the exquisite temporal and spatial expression patterns of thousands of genes during development-making sense of it all is a major challenge in the field. The study by Yakoby and colleagues illustrates how very different expression patterns can be generated from a small number of initial patterns. By examining expression patterns for a large number of genes in the Drosophila follicle cell epithelium, the authors proposed that the various expression patterns could be explained by a simple combinatorial code based on six spatial building blocks and the operations of union, difference, intersection, and addition. Importantly, the six spatial building block... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345920 Tue, 18 Oct 2011 04:00:00 +0100 5345920 http://www.medworm.com/index.php?rid=5345919&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014529%26dopt%3DAbstract This study illustrates how the combination of innovative genetic mouse models, embryological experimentation, and live-imaging techniques can resolve longstanding questions in endoderm formation during early mouse development. Kwon et al. showed that cells recruited from the epiblast during germ layer formation in the mouse embryo are not always incorporated into the endoderm in the immediate vicinity of the primitive streak. Beyond demonstrating that the mouse is just like a chick in its strategy for definitive (gut) endoderm recruitment, this finding resolved the enigmatic observation that some epiblast-derived cells in the endoderm are localized further from the site of ingression than anticipated based on "conventional" wisdom. Through tracking of the distribution of the visceral endo... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345919 Tue, 18 Oct 2011 04:00:00 +0100 5345919 http://www.medworm.com/index.php?rid=5345934&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22000856%26dopt%3DAbstract We present the crystal structure of the Dkk1 C-terminal domain bound to LRP6(3-4), and show that the Dkk1 N-terminal domain binds to LRP6(1-2), demonstrating that a single Dkk1 molecule can bind to both portions of the LRP6 ectodomain and thereby inhibit different Wnts. Small-angle X-ray scattering analysis of LRP6(1-4) bound to a noninhibitory antibody fragment or to full-length Dkk1 shows that in both cases the ectodomain adopts a curved conformation that places the first three repeats at a similar height relative to the membrane. Thus, Wnts bound to either portion of the LRP6 ectodomain likely bear a similar spatial relationship to Frizzled coreceptors. PMID: 22000856 [PubMed - as supplied by publisher] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345934 Wed, 12 Oct 2011 04:00:00 +0100 5345934 http://www.medworm.com/index.php?rid=5345935&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22000855%26dopt%3DAbstract Authors: Chen S, Bubeck D, Macdonald BT, Liang WX, Mao JH, Malinauskas T, Llorca O, Aricescu AR, Siebold C, He X, Jones EY Abstract LDL-receptor-related protein 6 (LRP6), alongside Frizzled receptors, transduces Wnt signaling across the plasma membrane. The LRP6 ectodomain comprises four tandem β-propeller-EGF-like domain (PE) pairs that harbor binding sites for Wnt morphogens and their antagonists including Dickkopf 1 (Dkk1). To understand how these multiple interactions are integrated, we combined crystallographic analysis of the third and fourth PE pairs with electron microscopy (EM) to determine the complete ectodomain structure. An extensive inter-pair interface, conserved for the first-to-second and third-to-fourth PE interactions, contributes to a compact platform-like arch... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5345935 Tue, 11 Oct 2011 04:00:00 +0100 5345935 http://www.medworm.com/index.php?rid=5313253&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982646%26dopt%3DAbstract Authors: Ferretti E, Li B, Zewdu R, Wells V, Hebert JM, Karner C, Anderson MJ, Williams T, Dixon J, Dixon MJ, Depew MJ, Selleri L Abstract Morphogenesis of mammalian facial processes requires coordination of cellular proliferation, migration, and apoptosis to develop intricate features. Cleft lip and/or palate (CL/P), the most frequent human craniofacial birth defect, can be caused by perturbation of any of these programs. Mutations of WNT, P63, and IRF6 yield CL/P in humans and mice; however, how these genes are regulated remains elusive. We generated mouse lines lacking Pbx genes in cephalic ectoderm and demonstrated that they exhibit fully penetrant CL/P and perturbed Wnt signaling. We also characterized a midfacial regulatory element that Pbx proteins bind to control the expre... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5313253 Tue, 04 Oct 2011 04:00:00 +0100 5313253 http://www.medworm.com/index.php?rid=5313254&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982645%26dopt%3DAbstract Authors: Bass MD, Williamson RC, Nunan RD, Humphries JD, Byron A, Morgan MR, Martin P, Humphries MJ Abstract Cell migration during wound healing requires adhesion receptor turnover to enable the formation and disassembly of cell-extracellular matrix contacts. Although recent advances have improved our understanding of integrin trafficking pathways, it is not known how extracellular ligand engagement controls receptor dynamics. Using atomic force microscopy, we have measured cell avidity for fibronectin and defined a mechanism for the outside-in regulation of α(5)β(1)-integrin. Surprisingly, adhesive strength was attenuated by the syndecan-4-binding domain of fibronectin due to a rapid triggering of α(5)β(1)-integrin endocytosis. Association of syndecan-4 with PKCα was found to... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5313254 Mon, 03 Oct 2011 04:00:00 +0100 5313254 http://www.medworm.com/index.php?rid=5313256&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962902%26dopt%3DAbstract Authors: Marhavý P, Bielach A, Abas L, Abuzeineh A, Duclercq J, Tanaka H, Pařezová M, Petrášek J, Friml J, Kleine-Vehn J, Benková E Abstract Cytokinin is an important regulator of plant growth and development. In Arabidopsis thaliana, the two-component phosphorelay mediated through a family of histidine kinases and response regulators is recognized as the principal cytokinin signal transduction mechanism activating the complex transcriptional response to control various developmental processes. Here, we identified an alternative mode of cytokinin action that uses endocytic trafficking as a means to direct plant organogenesis. This activity occurs downstream of known cytokinin receptors but through a branch of the cytokinin signaling pathway that does not involve transcription... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5313256 Wed, 28 Sep 2011 04:00:00 +0100 5313256 http://www.medworm.com/index.php?rid=5313255&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962903%26dopt%3DAbstract Authors: van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, Marks MS, Rubinstein E, Raposo G Abstract Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is required for lysosome-related organelle (LRO) biogenesis. PMEL-a component of melanocyte LROs (melanosomes)-is sorted to ILVs in an ESCRT-independent manner, where it is proteolytically processed and assembled into functional amyloid fibrils during melanosome maturation. Here we show that the tetraspanin CD63 directly participates in ESCRT-independent sorting of the PMEL luminal domain, but not of traditional ESCRT-dependent cargoes, to ILVs. Inactivating CD63 in cell culture or in mice impairs amyloidogenesis and downstream melanosome morphogenesis. Whereas CD63 is required for normal PMEL lumi... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5313255 Wed, 28 Sep 2011 04:00:00 +0100 5313255 http://www.medworm.com/index.php?rid=5281424&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21944719%26dopt%3DAbstract We report that mitofilin plays a dual role. Mitofilin is part of a large inner membrane complex, and we identify five partner proteins as constituents of the mitochondrial inner membrane organizing system (MINOS) that is required for keeping cristae membranes connected to the inner boundary membrane. Additionally, mitofilin is coupled to the outer membrane and promotes protein import via the mitochondrial intermembrane space assembly pathway. Our findings indicate that mitofilin is a central component of MINOS and functions as a multifunctional regulator of mitochondrial architecture and protein biogenesis. PMID: 21944719 [PubMed - as supplied by publisher] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5281424 Wed, 21 Sep 2011 04:00:00 +0100 5281424 http://www.medworm.com/index.php?rid=5281423&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21944720%26dopt%3DAbstract Authors: Odajima J, Wills ZP, Ndassa YM, Terunuma M, Kretschmannova K, Deeb TZ, Geng Y, Gawrzak S, Quadros IM, Newman J, Das M, Jecrois ME, Yu Q, Li N, Bienvenu F, Moss SJ, Greenberg ME, Marto JA, Sicinski P Abstract Cyclin E is a component of the core cell cycle machinery, and it drives cell proliferation by regulating entry and progression of cells through the DNA synthesis phase. Cyclin E expression is normally restricted to proliferating cells. However, high levels of cyclin E are expressed in the adult brain. The function of cyclin E in quiescent, postmitotic nervous system remains unknown. Here we use a combination of in vivo quantitative proteomics and analyses of cyclin E knockout mice to demonstrate that in terminally differentiated neurons cyclin E forms complexes with C... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5281423 Wed, 21 Sep 2011 04:00:00 +0100 5281423 http://www.medworm.com/index.php?rid=5247384&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21924960%26dopt%3DAbstract Authors: Li A, Ma Y, Yu X, Mort RL, Lindsay CR, Stevenson D, Strathdee D, Insall RH, Chernoff J, Snapper SB, Jackson IJ, Larue L, Sansom OJ, Machesky LM Abstract During embryogenesis, melanoblasts proliferate and migrate ventrally through the developing dermis and epidermis as single cells. Targeted deletion of Rac1 in melanoblasts during embryogenesis causes defects in migration, cell-cycle progression, and cytokinesis. Rac1 null cells migrate markedly less efficiently, but surprisingly, global steering, crossing the dermal/epidermal junction, and homing to hair follicles occur normally. Melanoblasts navigate in the epidermis using two classes of protrusion: short stubs and long pseudopods. Short stubs are distinct from blebs and are driven by actin assembly but are independent ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5247384 Tue, 13 Sep 2011 04:00:00 +0100 5247384 http://www.medworm.com/index.php?rid=5247383&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21924961%26dopt%3DAbstract Authors: Mammoto T, Mammoto A, Torisawa YS, Tat T, Gibbs A, Derda R, Mannix R, de Bruijn M, Yung CW, Huh D, Ingber DE Abstract Mesenchymal condensation is critical for organogenesis, yet little is known about how this process is controlled. Here we show that Fgf8 and Sema3f, produced by early dental epithelium, respectively, attract and repulse mesenchymal cells, which cause them to pack tightly together during mouse tooth development. Resulting mechanical compaction-induced changes in cell shape induce odontogenic transcription factors (Pax9, Msx1) and a chemical cue (BMP4), and mechanical compression of mesenchyme is sufficient to induce tooth-specific cell fate switching. The inductive effects of cell compaction are mediated by suppression of the mechanical signaling molecule Rh... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5247383 Tue, 13 Sep 2011 04:00:00 +0100 5247383 http://www.medworm.com/index.php?rid=5231705&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920303%26dopt%3DAbstract Authors: Millar SE Abstract Knockout mice are the gold standard for understanding gene function-or are they? The phenotypes of Egfl7 knockout mice and morphant fish suggested a critical and unexpected role for this secreted protein in angiogenesis, but a highly conserved microRNA, miR-126, was subsequently found in intron 7 of the Egfl7 gene. Wang et al. used gene targeting to knock out miR-126, but not Egfl7, and found that loss of miR-126 alone causes defects in embryonic and postnatal angiogenesis. These observations suggested that miR-126, rather than Egfl7, is the key player in angiogenesis, a result confirmed in a parallel study by Kuhnert et al. (2008), who generated mice specifically lacking Egfl7, but not miR-126, and vice versa. The intimate spatial and transcriptional ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231705 Tue, 13 Sep 2011 04:00:00 +0100 5231705 http://www.medworm.com/index.php?rid=5231704&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920304%26dopt%3DAbstract Authors: Harvey R Abstract The paper by Kelly et al., from Margaret Buckingham's group at the Pasteur Institute in Paris, changed the way we think about the developing mammalian heart, as well as the origins of congenital heart disease. Prior to this work, classical studies showing that the heart tube grows in part by the transformation of a noncardiac epithelium into cardiomyocytes had lapsed into obscurity. Kelly et al. and other papers have reinstated the notion that heart growth and morphogenesis are highly dynamic and driven by the recruitment of multipotent heart progenitor cells to a primitive scaffold. It was as if a light went on in the heart development field. This and subsequent work, much of it from Buckingham and colleagues, allows us to understand the cellular and m... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231704 Tue, 13 Sep 2011 04:00:00 +0100 5231704 http://www.medworm.com/index.php?rid=5231703&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920305%26dopt%3DAbstract Authors: Zuchero JB, Barres BA Abstract Myelin is a lipid-rich, spiraled membrane structure that allows for rapid propagation of action potentials through axons. In this issue, Aggarwal et al. (2011) present evidence that myelin basic protein, essential for myelination by oligodendrocytes, regulates the biosynthesis of myelin membranes by restricting diffusion of membrane-bound proteins into compact myelin. PMID: 21920305 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231703 Tue, 13 Sep 2011 04:00:00 +0100 5231703 http://www.medworm.com/index.php?rid=5231700&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920306%26dopt%3DAbstract Authors: Maia AR, Maiato H Abstract Mitochondria proliferate by growth and partition during every cell-division cycle. Recently, Kashatus et al. (2011) reported that Aurora A kinase regulates the small GTPase RalA to mediate mitochondrial fission. This work illuminates the molecular mechanism behind mitochondrial inheritance in mammals and extends the functional repertoire of a key mitotic regulator. PMID: 21920306 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231700 Tue, 13 Sep 2011 04:00:00 +0100 5231700 http://www.medworm.com/index.php?rid=5231699&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920307%26dopt%3DAbstract Authors: Gurudatta BV, Corces VG Abstract CTCF plays diverse roles in nuclear organization and transcriptional regulation. In this issue of Developmental Cell, Essafi et al. (2011) report a mechanism by which the repressive or active state of chromatin in a domain defined by CTCF can be switched by the Wt1 transcription factor to regulate gene expression. PMID: 21920307 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231699 Tue, 13 Sep 2011 04:00:00 +0100 5231699 http://www.medworm.com/index.php?rid=5231656&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920308%26dopt%3DAbstract Authors: Singh K, Dilworth FJ Abstract Nuclear spatial organization of genes has emerged as an important determinant of their transcriptional activity. In this issue, Wang et al. (2011) show that the Msx1 homeoprotein induces a dramatic redistribution of Ezh2 and H3K27me3 to the nuclear periphery of muscle progenitor cells to repress transcription of developmentally regulated genes. PMID: 21920308 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231656 Tue, 13 Sep 2011 04:00:00 +0100 5231656 http://www.medworm.com/index.php?rid=5231655&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920309%26dopt%3DAbstract Authors: Drenckhahn JD Abstract Continuous developmental maturation of cardiomyocytes is essential to meet the functional and metabolic demands of the growing heart. A new study (Hom et al., 2011) reports that embryonic cardiomyocytes are influenced by mitochondrial maturation, such that closure of the mitochondrial permeability transition pore results in decreased levels of reactive oxygen species, thereby inducing differentiation. PMID: 21920309 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231655 Tue, 13 Sep 2011 04:00:00 +0100 5231655 http://www.medworm.com/index.php?rid=5231654&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920310%26dopt%3DAbstract Authors: Buckingham ME, Meilhac SM Abstract Reconstructing the lineage of cells is central to understanding development and is now also an important issue in stem cell research. Technological advances in genetically engineered permanent cell labeling, together with a multiplicity of fluorescent markers and sophisticated imaging, open new possibilities for prospective and retrospective clonal analysis. PMID: 21920310 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231654 Tue, 13 Sep 2011 04:00:00 +0100 5231654 http://www.medworm.com/index.php?rid=5231653&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920311%26dopt%3DAbstract Authors: Sandquist JC, Kita AM, Bement WM Abstract The spindle directs chromosome partitioning in eukaryotes and, for the last three decades, has been considered primarily a structure based on microtubules, microtubule motors, and other microtubule binding proteins. However, a surprisingly large body of both old and new studies suggests roles for actin filaments (F-actin) and myosins (F-actin-based motor proteins) in spindle assembly and function. Here we review these data and conclude that in several cases the evidence for the participation of F-actin and myosins in spindle function is very strong, and in the situations where it is less strong, there is nevertheless enough evidence to warrant further investigation. PMID: 21920311 [PubMed - in process] (Source: Developmental Ce... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231653 Tue, 13 Sep 2011 04:00:00 +0100 5231653 http://www.medworm.com/index.php?rid=5231652&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920312%26dopt%3DAbstract Authors: Liu F, Lu Y, Pieuchot L, Dhavale T, Jedd G Abstract A fundamental question in cell biology is how cells control organelle composition and abundance. Woronin bodies are fungal peroxisomes centered on a crystalline core of the self-assembled HEX protein. Despite using the canonical peroxisome import machinery for biogenesis, Woronin bodies are scarce compared to the overall peroxisome population. Here, we show that HEX oligomers promote the differentiation of a subpopulation of peroxisomes, which become enlarged and highly active in matrix protein import. HEX physically associates with the essential matrix import peroxin, PEX26, and promotes its enrichment in the membrane of differentiated peroxisomes. In addition, a PEX26 mutant that disrupts differentiation produces incre... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231652 Tue, 13 Sep 2011 04:00:00 +0100 5231652 http://www.medworm.com/index.php?rid=5231651&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920313%26dopt%3DAbstract Authors: Hom JR, Quintanilla RA, Hoffman DL, de Mesy Bentley KL, Molkentin JD, Sheu SS, Porter GA Abstract Although mature myocytes rely on mitochondria as the primary source of energy, the role of mitochondria in the developing heart is not well known. Here, we find that closure of the mitochondrial permeability transition pore (mPTP) drives maturation of mitochondrial structure and function and myocyte differentiation. Cardiomyocytes at embryonic day (E) 9.5, when compared to E13.5, displayed fragmented mitochondria with few cristae, a less-polarized mitochondrial membrane potential, higher reactive oxygen species (ROS) levels, and an open mPTP. Pharmacologic and genetic closing of the mPTP yielded maturation of mitochondrial structure and function, lowered ROS, and increased myo... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231651 Tue, 13 Sep 2011 04:00:00 +0100 5231651 http://www.medworm.com/index.php?rid=5231650&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920314%26dopt%3DAbstract Authors: Van Campenhout CA, Eitelhuber A, Gloeckner CJ, Giallonardo P, Gegg M, Oller H, Grant SG, Krappmann D, Ueffing M, Lickert H Abstract The Drosophila Discs large (Dlg) scaffolding protein acts as a tumor suppressor regulating basolateral epithelial polarity and proliferation. In mammals, four Dlg homologs have been identified; however, their functions in cell polarity remain poorly understood. Here, we demonstrate that the X-linked mental retardation gene product Dlg3 contributes to apical-basal polarity and epithelial junction formation in mouse organizer tissues, as well as to planar cell polarity in the inner ear. We purified complexes associated with Dlg3 in polarized epithelial cells, including proteins regulating directed trafficking and tight junction formation. Remark... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231650 Tue, 13 Sep 2011 04:00:00 +0100 5231650 http://www.medworm.com/index.php?rid=5231649&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920315%26dopt%3DAbstract Authors: Pyati UJ, Gjini E, Carbonneau S, Lee JS, Guo F, Jette CA, Kelsell DP, Look AT Abstract Endoplasmic reticulum (ER) stress triggers tissue-specific responses that culminate in either cellular adaptation or apoptosis, but the genetic networks distinguishing these responses are not well understood. Here we demonstrate that ER stress induced in the developing zebrafish causes rapid apoptosis in the brain, spinal cord, tail epidermis, lens, and epiphysis. Focusing on the tail epidermis, we uncover an apoptotic response that depends on Puma, but not on p53 or Chop. puma is transcriptionally activated during this ER stress response in a p53-independent manner, and is an essential mediator of epidermal apoptosis. We demonstrate that the p63 transcription factor is upregulated to in... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231649 Tue, 13 Sep 2011 04:00:00 +0100 5231649 http://www.medworm.com/index.php?rid=5231648&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920316%26dopt%3DAbstract Authors: Wang C, Li S, Januschke J, Rossi F, Izumi Y, Garcia-Alvarez G, Gwee SS, Soon SB, Sidhu HK, Yu F, Matsuzaki F, Gonzalez C, Wang H Abstract Drosophila neural stem cells, larval brain neuroblasts (NBs), align their mitotic spindles along the apical/basal axis during asymmetric cell division (ACD) to maintain the balance of self-renewal and differentiation. Here, we identified a protein complex composed of the tumor suppressor anastral spindle 2 (Ana2), a dynein light-chain protein Cut up (Ctp), and Mushroom body defect (Mud), which regulates mitotic spindle orientation. We isolated two ana2 alleles that displayed spindle misorientation and NB overgrowth phenotypes in larval brains. The centriolar protein Ana2 anchors Ctp to centrioles during ACD. The centriolar localization o... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231648 Tue, 13 Sep 2011 04:00:00 +0100 5231648 http://www.medworm.com/index.php?rid=5231647&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920317%26dopt%3DAbstract Authors: Sakuno T, Tanaka K, Hauf S, Watanabe Y Abstract During meiosis I, kinetochores of sister chromatids are juxtaposed or fused and mono-orient, while homologous chromosomes that are paired by chiasmata (bivalents) have to biorient. In the absence of chiasmata, biorientation of sister chromatids (univalents), which carries a risk of aneuploidy, has been occasionally detected in several species, including humans. We show in fission yeast that biorientation of fused sister kinetochores predominates during early prometaphase I. Without chiasmata, this undesirable biorientation of univalents persists and eventually evades the spindle assembly checkpoint, provoking abnormal anaphase. When univalents are connected by chiasmata or by an artificial tether, this erroneous attachment is... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231647 Tue, 13 Sep 2011 04:00:00 +0100 5231647 http://www.medworm.com/index.php?rid=5231646&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920318%26dopt%3DAbstract Authors: Acloque H, Ocaña OH, Matheu A, Rizzoti K, Wise C, Lovell-Badge R, Nieto MA Abstract In developing amniote embryos, the first epithelial-to-mesenchymal transition (EMT) occurs at gastrulation, when a subset of epiblast cells moves to the primitive streak and undergoes EMT to internalize and generate the mesoderm and the endoderm. We show that in the chick embryo this decision to internalize is mediated by reciprocal transcriptional repression of Snail2 and Sox3 factors. We also show that the relationship between Sox3 and Snail is conserved in the mouse embryo and in human cancer cells. In the embryo, Snail-expressing cells ingress at the primitive streak, whereas Sox3-positive cells, which are unable to ingress, ensure the formation of ectodermal derivatives. Thus, the sub... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231646 Tue, 13 Sep 2011 04:00:00 +0100 5231646 http://www.medworm.com/index.php?rid=5231645&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920319%26dopt%3DAbstract Authors: Ikeda Y, Kinoshita Y, Susaki D, Ikeda Y, Iwano M, Takayama S, Higashiyama T, Kakutani T, Kinoshita T Abstract In Arabidopsis, DEMETER (DME) DNA demethylase contributes to reprogramming of the epigenetic state of the genome in the central cell. However, other aspects of the active DNA demethylation processes remain elusive. Here we show that Arabidopsis SSRP1, known as an HMG domain-containing component of FACT histone chaperone, is required for DNA demethylation and for activation and repression of many parentally imprinted genes in the central cell. Although loss of DNA methylation releases silencing of the imprinted FWA-GFP, double ssrp1-3;met1-3 mutants surprisingly showed limited activation of maternal FWA-GFP in the central cell, and only became fully active after sev... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5231645 Tue, 13 Sep 2011 04:00:00 +0100 5231645 http://www.medworm.com/index.php?rid=5219265&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889421%26dopt%3DAbstract Authors: Medina DL, Fraldi A, Bouche V, Annunziata F, Mansueto G, Spampanato C, Puri C, Pignata A, Martina JA, Sardiello M, Palmieri M, Polishchuk R, Puertollano R, Ballabio A Abstract Lysosomes are cellular organelles primarily involved in degradation and recycling processes. During lysosomal exocytosis, a Ca(2+)-regulated process, lysosomes are docked to the cell surface and fuse with the plasma membrane (PM), emptying their content outside the cell. This process has an important role in secretion and PM repair. Here we show that the transcription factor EB (TFEB) regulates lysosomal exocytosis. TFEB increases the pool of lysosomes in the proximity of the PM and promotes their fusion with PM by raising intracellular Ca(2+) levels through the activation of the lysosomal Ca(2+) cha... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5219265 Thu, 01 Sep 2011 04:00:00 +0100 5219265 http://www.medworm.com/index.php?rid=5193064&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21885353%26dopt%3DAbstract Authors: Aggarwal S, Yurlova L, Snaidero N, Reetz C, Frey S, Zimmermann J, Pähler G, Janshoff A, Friedrichs J, Müller DJ, Goebel C, Simons M Abstract The insulating layers of myelin membrane wrapped around axons by oligodendrocytes are essential for the rapid conduction of nerve impulses in the central nervous system. To fulfill this function as an electrical insulator, myelin requires a unique lipid and protein composition. Here we show that oligodendrocytes employ a barrier that functions as a physical filter to generate the lipid-rich myelin-membrane sheets. Myelin basic protein (MBP) forms this molecular sieve and restricts the diffusion of proteins with large cytoplasmic domains into myelin. The barrier is generated from MBP molecules that line the entire sheet and is, thus... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5193064 Mon, 29 Aug 2011 23:00:00 +0100 5193064 http://www.medworm.com/index.php?rid=5157519&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21852201%26dopt%3DAbstract Authors: Wang J, Kumar RM, Biggs VJ, Lee H, Chen Y, Kagey MH, Young RA, Abate-Shen C Abstract Control of gene expression during development requires the concerted action of sequence-specific transcriptional regulators and epigenetic modifiers, which are spatially coordinated within the nucleus through mechanisms that are poorly understood. Here we show that transcriptional repression by the Msx1 homeoprotein in myoblast cells requires the recruitment of Polycomb to target genes located at the nuclear periphery. Target genes repressed by Msx1 display an Msx1-dependent enrichment of Polycomb-directed trimethylation of lysine 27 on histone H3 (H3K27me3). Association of Msx1 with the Polycomb complex is required for repression and regulation of myoblast differentiation. Furthermore, Ms... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5157519 Tue, 16 Aug 2011 23:00:00 +0100 5157519 http://www.medworm.com/index.php?rid=5157518&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856246%26dopt%3DAbstract Authors: Wang T, Liu Y, Xu XH, Deng CY, Wu KY, Zhu J, Fu XQ, He M, Luo ZG Abstract Directed membrane trafficking is believed to be crucial for axon development during neuronal morphogenesis. However, the underlying mechanisms are poorly understood. Here, we report a role of Lgl1, the mammalian homolog of Drosophila tumor suppressor Lethal giant larvae, in controlling membrane trafficking underlying axonal growth. We find that Lgl1 is associated with plasmalemmal precursor vesicles and enriched in developing axons. Lgl1 upregulation promoted axonal growth, whereas downregulation attenuated it as well as directional membrane insertion. Interestingly, Lgl1 interacted with and activated Rab10, a small GTPase that mediates membrane protein trafficking, by releasing GDP dissociation inhi... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5157518 Tue, 16 Aug 2011 23:00:00 +0100 5157518 http://www.medworm.com/index.php?rid=5141640&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820362%26dopt%3DAbstract Authors: Lee FY, Faivre EJ, Suzawa M, Lontok E, Ebert D, Cai F, Belsham DD, Ingraham HA Abstract Sumoylation is generally considered a repressive mark for many transcription factors. However, the in vivo importance of sumoylation for any given substrate remains unclear and is questionable because the extent of sumoylation appears exceedingly low for most substrates. Here, we permanently eliminated SF-1/NR5A1 sumoylation in mice (Sf-1(K119R)(, K194R, or 2KR)) and found that Sf-1(2KR/2KR) mice failed to phenocopy a simple gain of SF-1 function or show elevated levels of well-established SF-1 target genes. Instead, mutant mice exhibited marked endocrine abnormalities and changes in cell fate that reflected an inappropriate activation of hedgehog signaling and other potential SUMO-sen... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141640 Mon, 15 Aug 2011 23:00:00 +0100 5141640 http://www.medworm.com/index.php?rid=5141639&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820363%26dopt%3DAbstract Authors: Vagnarelli P, Ribeiro S, Sennels L, Sanchez-Pulido L, de Lima Alves F, Verheyen T, Kelly DA, Ponting CP, Rappsilber J, Earnshaw WC Abstract Repo-Man targets protein phosphatase 1 γ (PP1γ) to chromatin at anaphase onset and regulates chromosome structure during mitotic exit. Here, we show that a Repo-Man:PP1 complex forms in anaphase following dephosphorylation of Repo-Man. Upon activation, the complex localizes to chromosomes and causes the dephosphorylation of histone H3 (Thr3, Ser10, and Ser28). In anaphase, Repo-Man has both catalytic and structural functions that are mediated by two separate domains. A C-terminal domain localizes Repo-Man to bulk chromatin in early anaphase. There, it targets PP1 for the dephosphorylation of histone H3 and possibly other chromosomal ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141639 Mon, 15 Aug 2011 23:00:00 +0100 5141639 http://www.medworm.com/index.php?rid=5141638&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839911%26dopt%3DAbstract Authors: Hicke L Abstract A paper from Itoh et al. has stuck with me since its publication date 8 years ago for many reasons, but primarily because it stretched my mind and pleased my eye. The major conclusion of the paper-that Mind bomb-mediated ubiquitination of Delta promotes its endocytosis, thereby activating Notch signaling in an adjacent cell-was an important advance in the fields of ubiquitin-mediated regulation, Delta-Notch activated signaling, and neuronal development. For these reasons the title and abstract caught my attention. However, this manuscript was a challenging read for a life-long yeast cell biologist. I had heard talks over the years from my developmental biology colleagues, but I wasn't used to looking carefully at zebrafish embryos. I had also never rigoro... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141638 Mon, 15 Aug 2011 23:00:00 +0100 5141638 http://www.medworm.com/index.php?rid=5141637&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839912%26dopt%3DAbstract Authors: Ingham PW Abstract I like this paper because the findings that it reports took me completely by surprise-and serve as a constant reminder of the fallibility of my own scientific logic! A few years earlier, Rune Toftgård had invited me to give a talk at the Karolinska Institute about our analysis of the Hedgehog (HH) signaling pathway in Drosophila. During the course of my visit, Rune told me that he and his colleagues were planning to make a mouse knockout mutation of the Suppressor of fused (SUFU) gene, an exercise that I opined would be of only marginal value, given the dispensable nature of the orthologous gene in Drosophila. Indeed, my skepticism seemed well placed when we subsequently found that morpholino-mediated knockdown of SUFU has a rather subtle effect on HH ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141637 Mon, 15 Aug 2011 23:00:00 +0100 5141637 http://www.medworm.com/index.php?rid=5141636&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839913%26dopt%3DAbstract Authors: Theurkauf W Abstract Transposons and fragments of transposable elements make up approximately half of the human genome; mobilization of these elements can destabilize the genome and lead to disease-associated mutations. In 2003, miRNAs and siRNAs were known to silence target mRNAs, but small RNAs had not been directly linked to transposon control. In August of that year, Aravin et al. reported the developmental profile of Drosophila small RNAs by using conventional sequencing technology. These pioneering studies identified a novel class of "repeat associated" siRNAs and hypothesized that they control transposon activity and chromatin structure. It is now clear that these "rasiRNAs" bind to Piwi clade Argonaute proteins and that Piwi-interacting RNAs (piRNAs) have a cons... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141636 Mon, 15 Aug 2011 23:00:00 +0100 5141636 http://www.medworm.com/index.php?rid=5141635&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839914%26dopt%3DAbstract Authors: Kalcheim C Abstract It is well established that the somitic mesoderm regulates early stages of neural crest development and further segmentation of crest-derived peripheral ganglia. The possibility that neural crest progenitors feed back on the somites was, however, not explored. Two recent studies provide evidence that the neural crest regulates somite-derived myogenesis by distinct mechanisms. PMID: 21839914 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141635 Mon, 15 Aug 2011 23:00:00 +0100 5141635 http://www.medworm.com/index.php?rid=5141634&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839915%26dopt%3DAbstract Authors: Tamagnone L, Mazzone M Abstract Blood vessels sprout toward avascular tissue in response to attractive proangiogenic factors. However, restricting signals are also required to coordinate the behavior of endothelial cells assembling the vascular network. Semaphorin cues are at the crossroad of this traffic, and they direct the behavior of endothelial tip cells leading the way. PMID: 21839915 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141634 Mon, 15 Aug 2011 23:00:00 +0100 5141634 http://www.medworm.com/index.php?rid=5141633&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839916%26dopt%3DAbstract Authors: Lin FM, Yeh ET Abstract When a transcription factor is modified by small ubiquitin-like modifier (SUMO), this usually represses its transcriptional activity. In this issue of Developmental Cell, Lee et al. (2011) use a knockin mouse model to show that SUMO-less SF-1 binds and activates inappropriate targets, causing changes in cell fates and endocrine abnormalities. PMID: 21839916 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141633 Mon, 15 Aug 2011 23:00:00 +0100 5141633 http://www.medworm.com/index.php?rid=5141632&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839917%26dopt%3DAbstract Authors: Armulik A, Genové G, Betsholtz C Abstract Pericytes, the mural cells of blood microvessels, have recently come into focus as regulators of vascular morphogenesis and function during development, cardiovascular homeostasis, and disease. Pericytes are implicated in the development of diabetic retinopathy and tissue fibrosis, and they are potential stromal targets for cancer therapy. Some pericytes are probably mesenchymal stem or progenitor cells, which give rise to adipocytes, cartilage, bone, and muscle. However, there is still confusion about the identity, ontogeny, and progeny of pericytes. Here, we review the history of these investigations, indicate emerging concepts, and point out problems and promise in the field of pericyte biology. PMID: 21839917 [PubMed - in ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141632 Mon, 15 Aug 2011 23:00:00 +0100 5141632 http://www.medworm.com/index.php?rid=5141631&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839918%26dopt%3DAbstract Authors: Chesarone-Cataldo M, Guérin C, Yu JH, Wedlich-Soldner R, Blanchoin L, Goode BL Abstract Formins are a conserved family of proteins with robust effects in promoting actin nucleation and elongation. However, the mechanisms restraining formin activities in cells to generate actin networks with particular dynamics and architectures are not well understood. In S. cerevisiae, formins assemble actin cables, which serve as tracks for myosin-dependent intracellular transport. Here, we show that the kinesin-like myosin passenger-protein Smy1 interacts with the FH2 domain of the formin Bnr1 to decrease rates of actin filament elongation, which is distinct from the formin displacement activity of Bud14. In vivo analysis of smy1Δ mutants demonstrates that this "damper" mechanism is... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141631 Mon, 15 Aug 2011 23:00:00 +0100 5141631 http://www.medworm.com/index.php?rid=5141630&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839919%26dopt%3DAbstract Authors: Pastor-Pareja JC, Xu T Abstract Basement membranes (BMs) are resilient polymer structures that surround organs in all animals. Tissues, however, undergo extensive morphological changes during development. It is not known whether the assembly of BM components plays an active morphogenetic role. To study in vivo the biogenesis and assembly of Collagen IV, the main constituent of BMs, we used a GFP-based RNAi method (iGFPi) designed to knock down any GFP-trapped protein in Drosophila. We found with this method that Collagen IV is synthesized by the fat body, secreted to the hemolymph (insect blood), and continuously incorporated into the BMs of the larva. We also show that incorporation of Collagen IV determines organ shape, first by mechanically constricting cells and secon... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141630 Mon, 15 Aug 2011 23:00:00 +0100 5141630 http://www.medworm.com/index.php?rid=5141629&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839920%26dopt%3DAbstract Authors: Shimokawa K, Kimura-Yoshida C, Nagai N, Mukai K, Matsubara K, Watanabe H, Matsuda Y, Mochida K, Matsuo I Abstract Heparan sulfate (HS) proteoglycans modulate the activity of multiple growth factors on the cell surface and extracellular matrix. However, it remains unclear how the HS chains control the movement and reception of growth factors into targeted receiving cells during mammalian morphogenetic processes. Here, we found that HS-deficient Ext2 null mutant mouse embryos fail to respond to fibroblast growth factor (FGF) signaling. Marker expression analyses revealed that cell surface-tethered HS chains are crucial for local retention of FGF4 and FGF8 ligands in the extraembryonic ectoderm. Fine chimeric studies with single-cell resolution and expression studies with spe... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141629 Mon, 15 Aug 2011 23:00:00 +0100 5141629 http://www.medworm.com/index.php?rid=5141628&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839921%26dopt%3DAbstract Authors: Chang AC, Fu Y, Garside VC, Niessen K, Chang L, Fuller M, Setiadi A, Smrz J, Kyle A, Minchinton A, Marra M, Hoodless PA, Karsan A Abstract The heart is the most common site of congenital defects, and valvuloseptal defects are the most common of the cardiac anomalies seen in the newborn. The process of endothelial-to-mesenchymal transition (EndMT) in the cardiac cushions is a required step during early valve development, and Notch signaling is required for this process. Here we show that Notch activation induces the transcription of both subunits of the soluble guanylyl cyclase (sGC) heterodimer, GUCY1A3 and GUCY1B3, which form the nitric oxide receptor. In parallel, Notch also promotes nitric oxide (NO) production by inducing Activin A, thereby activating a PI3-kinase/Akt ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141628 Mon, 15 Aug 2011 23:00:00 +0100 5141628 http://www.medworm.com/index.php?rid=5141627&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839922%26dopt%3DAbstract Authors: Suzuki K, Morimoto M, Kondo C, Ohsumi Y Abstract Macroautophagy (autophagy) is a bulk degradation system for cytoplasmic components and is ubiquitously found in eukaryotic cells. Autophagy is induced under starvation conditions and plays a cytoprotective role by degrading unwanted cytoplasmic materials. The Ty1 transposon, a member of the Ty1/copia superfamily, is the most abundant retrotransposon in the yeast Saccharomyces cerevisiae and acts to introduce mutations in the host genome via Ty1 virus-like particles (VLPs) localized in the cytoplasm. Here we show that selective autophagy downregulates Ty1 transposition by eliminating Ty1 VLPs from the cytoplasm under nutrient-limited conditions. Ty1 VLPs are targeted to autophagosomes by an interaction with Atg19. We propose ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141627 Mon, 15 Aug 2011 23:00:00 +0100 5141627 http://www.medworm.com/index.php?rid=5141626&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839923%26dopt%3DAbstract Authors: Vincent JP, Kolahgar G, Gagliardi M, Piddini E Abstract Wnt signaling is a key regulator of development that is often associated with cancer. Wingless, a Drosophila Wnt homolog, has been reported to be a survival factor in wing imaginal discs. However, we found that prospective wing cells survive in the absence of Wingless as long as they are not surrounded by Wingless-responding cells. Moreover, local autonomous overactivation of Wg signaling (as a result of a mutation in APC or axin) leads to the elimination of surrounding normal cells. Therefore, relative differences in Wingless signaling lead to competitive cell interactions. This process does not involve Myc, a well-established cell competition factor. It does, however, require Notum, a conserved secreted feedback i... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141626 Mon, 15 Aug 2011 23:00:00 +0100 5141626 http://www.medworm.com/index.php?rid=5141625&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839924%26dopt%3DAbstract Authors: Peluso CE, Umulis D, Kim YJ, O'Connor MB, Serpe M Abstract Bone morphogenetic proteins (BMPs) regulate dorsal/ventral (D/V) patterning across the animal kingdom; however, the biochemical properties of certain pathway components can vary according to species-specific developmental requirements. For example, Tolloid (Tld)-like metalloproteases cleave vertebrate BMP-binding proteins called Chordins constitutively, while the Drosophila Chordin ortholog, Short gastrulation (Sog), is only cleaved efficiently when bound to BMPs. We identified Sog characteristics responsible for making its cleavage dependent on BMP binding. "Chordin-like" variants that are processed independently of BMPs changed the steep BMP gradient found in Drosophila embryos to a shallower profile, analogous t... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5141625 Mon, 15 Aug 2011 23:00:00 +0100 5141625 http://www.medworm.com/index.php?rid=5104126&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802374%26dopt%3DAbstract Authors: Lu Q, Yang P, Huang X, Hu W, Guo B, Wu F, Lin L, Kovács AL, Yu L, Zhang H PtdIns(3)P plays critical roles in the autophagy pathway. However, little is known about how PtdIns(3)P effectors act with autophagy proteins in autophagosome formation. Here we identified an essential autophagy gene in C. elegans, epg-6, which encodes a WD40 repeat-containing protein with PtdIns(3)P-binding activity. EPG-6 directly interacts with ATG-2. epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures. Another WD40 repeat PtdIns(3)P effector, ATG-18, plays a distinct role in autophagosome formation. We also established the hierarchical relationship of autophagy genes in degradation of protein ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5104126 Tue, 26 Jul 2011 23:00:00 +0100 5104126 http://www.medworm.com/index.php?rid=5104125&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802375%26dopt%3DAbstract Authors: Zygmunt T, Gay CM, Blondelle J, Singh MK, Flaherty KM, Means PC, Herwig L, Krudewig A, Belting HG, Affolter M, Epstein JA, Torres-Vázquez J Sprouting angiogenesis expands the embryonic vasculature enabling survival and homeostasis. Yet how the angiogenic capacity to form sprouts is allocated among endothelial cells (ECs) to guarantee the reproducible anatomy of stereotypical vascular beds remains unclear. Here we show that Sema-PlxnD1 signaling, previously implicated in sprout guidance, represses angiogenic potential to ensure the proper abundance and stereotypical distribution of the trunk's segmental arteries (SeAs). We find that Sema-PlxnD1 signaling exerts this effect by antagonizing the proangiogenic activity of vascular endothelial growth factor (VEGF). Specifically, Se... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5104125 Tue, 26 Jul 2011 23:00:00 +0100 5104125 http://www.medworm.com/index.php?rid=5104128&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782525%26dopt%3DAbstract Authors: Ho AT, Hayashi S, Bröhl D, Auradé F, Rattenbach R, Relaix F Coordinating the balance between progenitor self-renewal and myogenic differentiation is required for a regulated expansion of the developing muscles. Previous observation that neural crest cells (NCCs) migrate throughout the somite regions, where trunk skeletal muscles first emerge, suggests a potential role for these cells in influencing early muscle formation. However, specific signaling interactions between NCCs and skeletal muscle cells remain unknown. Here we show that mice with specific NCC and peripheral nervous system defects display impaired survival of skeletal muscle and show skeletal muscle progenitor cell (MPC) depletion due to precocious commitment to differentiation. We show that reduced NCC-derived ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5104128 Tue, 19 Jul 2011 23:00:00 +0100 5104128 http://www.medworm.com/index.php?rid=5104127&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782526%26dopt%3DAbstract Authors: Moreau D, Kumar P, Wang SC, Chaumet A, Chew SY, Chevalley H, Bard F Protein toxins such as Ricin and Pseudomonas exotoxin (PE) pose major public health challenges. Both toxins depend on host cell machinery for internalization, retrograde trafficking from endosomes to the ER, and translocation to cytosol. Although both toxins follow a similar intracellular route, it is unknown how much they rely on the same genes. Here we conducted two genome-wide RNAi screens identifying genes required for intoxication and demonstrating that requirements are strikingly different between PE and Ricin, with only 13% overlap. Yet factors required by both toxins are present from the endosomes to the ER, and, at the morphological level, the toxins colocalize in multiple structures. Interestingly, ... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5104127 Tue, 19 Jul 2011 23:00:00 +0100 5104127 http://www.medworm.com/index.php?rid=5058155&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763596%26dopt%3DAbstract Authors: Wainstock DH PMID: 21763596 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058155 Mon, 18 Jul 2011 23:00:00 +0100 5058155 http://www.medworm.com/index.php?rid=5058154&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763597%26dopt%3DAbstract Authors: Little SC, Wieschaus EF We highlight crucial technological progress of the past ten years that permits quantitative analysis of cellular behavior. Adapting these methods to the study of embryogenesis will be essential to advance our understanding of development in the coming decade. PMID: 21763597 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058154 Mon, 18 Jul 2011 23:00:00 +0100 5058154 http://www.medworm.com/index.php?rid=5058153&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763598%26dopt%3DAbstract Authors: Lippincott-Schwartz J Many unexpected discoveries in developmental biology have depended on advancement of imaging technologies to visualize developmental processes as they unfold across multiple spatial and temporal scales. This essay surveys the recent advances in imaging, highlighting emerging capabilities with an eye toward those poised to have the greatest impact on developmental biology. PMID: 21763598 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058153 Mon, 18 Jul 2011 23:00:00 +0100 5058153 http://www.medworm.com/index.php?rid=5058152&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763599%26dopt%3DAbstract Authors: El-Samad H, Madhani HD The study of dramatic phenotypes has been pivotal to elucidating biological mechanisms. Effectively approaching low-magnitude quantitative phenotypes, a common outcome of systematic loss-of-function studies, will be critical for understanding how individual components of cells interact to generate functioning systems. PMID: 21763599 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058152 Mon, 18 Jul 2011 23:00:00 +0100 5058152 http://www.medworm.com/index.php?rid=5058151&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763600%26dopt%3DAbstract Authors: Hyman AA, Brangwynne CP The cytoplasm is not a homogenous solution but instead consists of large dynamic assemblies that arise from transient molecular interactions. Some of these structures have been shown to represent liquid droplets of concentrated protein and RNA. Liquid phase separation of cytoplasm may be a fundamental principle of cytoplasmic organization. PMID: 21763600 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058151 Mon, 18 Jul 2011 23:00:00 +0100 5058151 http://www.medworm.com/index.php?rid=5058150&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763601%26dopt%3DAbstract Authors: Williamson I, Hill RE, Bickmore WA In mammals, long-range gene regulation became apparent through simple Mendelian disease genetics in human and developmental genetics in the mouse. Can the insights into gene control, provided by the study of these enhancers, help us understand the functional significance of sequence variation associated with common/complex human disease and quantitative traits? PMID: 21763601 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058150 Mon, 18 Jul 2011 23:00:00 +0100 5058150 http://www.medworm.com/index.php?rid=5058149&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763602%26dopt%3DAbstract Authors: Rossant J Research on developmental pathways in model organisms provides key information on how to isolate, maintain, and differentiate human pluripotent stem cells. However, details of developmental pathways differ even across mammalian species. Full realization of the potential of stem cells will require more direct studies of human or primate developmental biology. PMID: 21763602 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058149 Mon, 18 Jul 2011 23:00:00 +0100 5058149 http://www.medworm.com/index.php?rid=5058148&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763603%26dopt%3DAbstract Authors: Takeichi M Animal cells are capable of self-organizing into multicellular tissues, and important players in this process are cadherin receptors. Through the homophilic interactions of cadherins, cells adhere to one another. Cells can also dynamically change shapes or positions within tissue layers via cadherin-cytoskeleton interactions and become arranged into various architectures. PMID: 21763603 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058148 Mon, 18 Jul 2011 23:00:00 +0100 5058148 http://www.medworm.com/index.php?rid=5058147&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763604%26dopt%3DAbstract Authors: Benfey PN Developmental biologists understand how different cells contribute to organ function and how cellular components work together to produce a phenotype. These insights need to be more widely applied to systems biology. Another challenge is to incorporate real-time imaging and develop computational approaches to model biological phenomena in four dimensions. PMID: 21763604 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058147 Mon, 18 Jul 2011 23:00:00 +0100 5058147 http://www.medworm.com/index.php?rid=5058146&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763605%26dopt%3DAbstract Authors: Rajan A, Perrimon N Current studies of physiological communication between Drosophila organs are beginning to address the fundamental problem of how nutrients regulate organismal growth, stem cell behavior, immunity, and aging. Advances in the Drosophila genetic tool kit will allow the design of genetic screens to systematically identify factors involved in organ communication. PMID: 21763605 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058146 Mon, 18 Jul 2011 23:00:00 +0100 5058146 http://www.medworm.com/index.php?rid=5058145&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763606%26dopt%3DAbstract Authors: Dickinson DJ, Weis WI, Nelson WJ Studies of animal evolution often focus on sequence and transcriptional analysis, based on an assumption that the evolution of development is driven by changes in gene expression. We argue that biochemical and cell biological approaches are also required, because sequence-conserved proteins can have different biochemical, cellular, and developmental properties. PMID: 21763606 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058145 Mon, 18 Jul 2011 23:00:00 +0100 5058145 http://www.medworm.com/index.php?rid=5058144&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763607%26dopt%3DAbstract Authors: Eyckmans J, Boudou T, Yu X, Chen CS More than a century ago, it was proposed that mechanical forces could drive tissue formation. However, only recently with the advent of enabling biophysical and molecular technologies are we beginning to understand how individual cells transduce mechanical force into biochemical signals. In turn, this knowledge of mechanotransduction at the cellular level is beginning to clarify the role of mechanics in patterning processes during embryonic development. In this perspective, we will discuss current mechanotransduction paradigms, along with the technologies that have shaped the field of mechanobiology. PMID: 21763607 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058144 Mon, 18 Jul 2011 23:00:00 +0100 5058144 http://www.medworm.com/index.php?rid=5058143&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763608%26dopt%3DAbstract Authors: Lawson ND, Wolfe SA The development of facile forward and reverse genetic approaches has propelled the deconvolution of gene function in biology. While the origins of these techniques reside in the study of single-cell or invertebrate organisms, in many cases these approaches have been applied to vertebrate model systems to gain powerful insights into gene function during embryonic development. This perspective provides a summary of the major forward and reverse genetic approaches that have contributed to the study of vertebrate gene function in zebrafish, which has become an established model for the study of animal development. PMID: 21763608 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058143 Mon, 18 Jul 2011 23:00:00 +0100 5058143 http://www.medworm.com/index.php?rid=5058142&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763609%26dopt%3DAbstract Authors: Rowan BA, Weigel D, Koenig D Much of developmental biology in the past decades has been driven by forward genetic studies in a few model organisms. We review recent work with relatives of these species, motivated by a desire to understand the evolutionary and ecological context for morphological innovation. Unfortunately, despite a number of shining examples, progress in nonmodel systems has often been slow. The current revolution in DNA sequencing has, however, enormous potential in extending the reach of genetics. We discuss how developmental biology will benefit from these advances, particularly by increasing the universe of study species. PMID: 21763609 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058142 Mon, 18 Jul 2011 23:00:00 +0100 5058142 http://www.medworm.com/index.php?rid=5058141&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763610%26dopt%3DAbstract Authors: Henne WM, Buchkovich NJ, Emr SD Multivesicular bodies (MVBs) deliver cargo destined for degradation to the vacuole or lysosome. The ESCRT (endosomal sorting complex required for transport) pathway is a key mediator of MVB biogenesis, but it also plays critical roles in retroviral budding and cytokinetic abscission. Despite these diverse roles, the ESCRT pathway can be simply seen as a cargo-recognition and membrane-sculpting machine viewable from three distinct perspectives: (1) the ESCRT proteins themselves, (2) the cargo they sort, and (3) the membrane they deform. Here, we review ESCRT function from these perspectives and discuss how ESCRTs may drive vesicle budding. PMID: 21763610 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058141 Mon, 18 Jul 2011 23:00:00 +0100 5058141 http://www.medworm.com/index.php?rid=5058140&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763611%26dopt%3DAbstract Authors: Martinou JC, Youle RJ Mitochondria participate in apoptosis through a range of mechanisms that vary between vertebrates and invertebrates. In vertebrates, they release intermembrane space proteins, such as cytochrome c, to promote caspase activation in the cytosol. This process is the result of the loss of integrity of the outer mitochondrial membrane caused by proapoptotic members of the Bcl-2 family. This event is always accompanied by a fissioning of the organelle. Fission of mitochondria has also been reported to participate in apoptosis in Drosophila and Caenorhabditis elegans. However, in these organisms, mitochondrial membrane permeabilization does not occur and the mechanism by which mitochondrial dynamics participates in cell death remains elusive. PMID: 21763611... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058140 Mon, 18 Jul 2011 23:00:00 +0100 5058140 http://www.medworm.com/index.php?rid=5058139&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763612%26dopt%3DAbstract Authors: Morin X, Bellaïche Y The orientation of the mitotic spindle has been proposed to control cell fate choices, tissue architecture, and tissue morphogenesis. Here, we review the mechanisms regulating the orientation of the axis of division and cell fate choices in classical models of asymmetric cell division. We then discuss the mechanisms of mitotic spindle orientation in symmetric cell divisions and its possible implications in tissue morphogenesis. Many recent studies show that future advances in the field of mitotic spindle orientation will arise from combinations of physical perturbation and modeling with classical genetics and developmental biology approaches. PMID: 21763612 [PubMed - in process] (Source: Developmental Cell) Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058139 Mon, 18 Jul 2011 23:00:00 +0100 5058139 http://www.medworm.com/index.php?rid=5058138&cid=s_35511_171_f&fid=35511&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763613%26dopt%3DAbstract Authors: Gray RS, Roszko I, Solnica-Krezel L Planar cell polarization entails establishment of cellular asymmetries within the tissue plane. An evolutionarily conserved planar cell polarity (PCP) signaling system employs intra- and intercellular feedback interactions between its core components, including Frizzled, Van Gogh, Flamingo, Prickle, and Dishevelled, to establish their characteristic asymmetric intracellular distributions and coordinate planar polarity of cell populations. By translating global patterning information into asymmetries of cell membranes and intracellular organelles, PCP signaling coordinates morphogenetic behaviors of individual cells and cell populations with the embryonic polarity. In vertebrates, by polarizing cilia in the node/Kupffer's vesicle, PCP signali... Developmental Cell journals http://www.medworm.com/rss/comments.php?id=5058138 Mon, 18 Jul 2011 23:00:00 +0100 5058138