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Special Features and New Developments.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19922861 [PubMed - as supplied by publisher] (Source: Developmental Cell)
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Sweet DJ Tags: Dev Cell Source Type: journals

Sorting Out Endosomes in the WASH.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Two new studies published in this issue of Developmental Cell by Derivery et al. and Gomez and Billadeau reveal that WASH (Wiskott-Aldrich syndrome protein and SCAR homolog) activates Arp2/3 on endosomes and plays a critical role in the fission of tubules that serve as transport intermediates during endosome sorting. PMID: 19922862 [PubMed - as supplied by publisher] (Source: Developmental Cell)
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Bear JE Tags: Dev Cell Source Type: journals

Developmental ECM Sculpting: Laying It Down and Cutting It Up.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In mammals, proteolytic remodeling of the embryonic extracellular matrix (ECM) controls morphogenesis, but the key players remain elusive. Two recent reports identify new roles for metalloproteinases belonging to the MT-MMP and ADAMTS families in branching morphogenesis and interdigital web regression. PMID: 19922863 [PubMed - as supplied by publisher] (Source: Developmental Cell)
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Feinberg T, Weiss SJ Tags: Dev Cell Source Type: journals

Nuclei Take a Position: Managing Nuclear Location.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Eukaryotic cells display considerable morphological plasticity linked to their abilities to carry out a myriad of complex functions. Structural rearrangements associated with cellular activities, from yeast mitosis to cell migration in the mammalian central nervous system, often involve relocation of the cell nucleus. Recent studies have provided insight into how nuclear components can be mechanically coupled to the cytoskeleton, providing a more complete understanding of the role of nuclear positioning in both health and disease. PMID: 19922864 [PubMed - as supplied by publisher] (Source: Developmental Cell)
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Burke B, Roux KJ Tags: Dev Cell Source Type: journals

The SUN Rises on Meiotic Chromosome Dynamics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent studies in diverse eukaryotes have implicated a family of nuclear envelope proteins containing SUN domains as key components of meiotic nuclear organization and chromosome dynamics. In many cases, these transmembrane proteins are also known to contribute to centrosome or spindle pole body function in mitotically dividing cells. During meiotic prophase, the apparent role of these SUN-domain proteins, together with their partner KASH-domain proteins, is to connect chromosomes through the intact nuclear envelope to force-generating mechanisms in the cytoplasm. PMID: 19922865 [PubMed - as supplied by publisher] ...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Hiraoka Y, Dernburg AF Tags: Dev Cell Source Type: journals

Border Control at the Nucleus: Biogenesis and Organization of the Nuclear Membrane and Pore Complexes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Over the last decade, the nuclear envelope (NE) has emerged as a key component in the organization and function of the nuclear genome. As many as 100 different proteins are thought to specifically localize to this double membrane that separates the cytoplasm and the nucleoplasm of eukaryotic cells. Selective portals through the NE are formed at sites where the inner and outer nuclear membranes are fused, and the coincident assembly of approximately 30 proteins into nuclear pore complexes occurs. These nuclear pore complexes are essential for the control of nucleocytoplasmic exchange. Many of the NE and nuclear pore pro...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Hetzer MW, Wente SR Tags: Dev Cell Source Type: journals

Acting Out of Character: Regulatory Roles of Nuclear Pore Complex Proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nuclear pore complexes (NPCs) mediate all selective bidirectional transport between the nucleus and the cytoplasm. Additional functions for NPCs and their constituent proteins (nucleoporins) are emerging, some independent of classical transport. Specifically, enzymatic activities at the NPC regulate nucleocytoplasmic transport and use the NPC as a regulatory scaffold. Also, nucleoporins may regulate gene expression by contacting chromatin. Discriminating between effects on transport, scaffolding, and gene expression is a major challenge in understanding the role of the NPC in signaling and development. PMID: 199228...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Xylourgidis N, Fornerod M Tags: Dev Cell Source Type: journals

The Nuclear Envelope as a Signaling Node in Development and Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The development of a membrane-bound structure separating DNA from other cellular components was the epochal evolutionary event that gave rise to eukaryotes, possibly occurring up to 2 billion years ago. Yet, this view of the nuclear envelope as a physical barrier greatly underestimates its fundamental impact on cellular organization and complexity, much of which is only beginning to be understood. Indeed, alterations of nuclear envelope structure and protein composition are essential to many aspects of metazoan development and cellular differentiation. Mutations in genes encoding nuclear envelope proteins cause a fasci...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Dauer WT, Worman HJ Tags: Dev Cell Source Type: journals

Nuclear Bodies: Random Aggregates of Sticky Proteins or Crucibles of Macromolecular Assembly?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The principles of self-assembly and self-organization are major tenets of molecular and cellular biology. Governed by these principles, the eukaryotic nucleus is composed of numerous subdomains and compartments, collectively described as nuclear bodies. Emerging evidence reveals that associations within and between various nuclear bodies and genomic loci are dynamic and can change in response to cellular signals. This review will discuss recent progress in our understanding of how nuclear body components come together, what happens when they form, and what benefit these subcellular structures may provide to the tissues...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Matera AG, Izaguire-Sierra M, Praveen K, Rajendra TK Tags: Dev Cell Source Type: journals

MOR23 Promotes Muscle Regeneration and Regulates Cell Adhesion and Migration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. Mouse OR23 (MOR23) expression is induced during muscle regeneration when muscle cells are extensively fusing and plays a key role in regulating migration and adhesion of muscle cells in vitro, two processes common during tissue repair. A soluble ligand for MOR23 is secreted by muscle cells in vitro and mus...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Griffin CA, Kafadar KA, Pavlath GK Tags: Dev Cell Source Type: journals

A Family of microRNAs Encoded by Myosin Genes Governs Myosin Expression and Muscle Performance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Myosin is the primary regulator of muscle strength and contractility. Here we show that three myosin genes, Myh6, Myh7, and Myh7b, encode related intronic microRNAs (miRNAs), which, in turn, control muscle myosin content, myofiber identity, and muscle performance. Within the adult heart, the Myh6 gene, encoding a fast myosin, coexpresses miR-208a, which regulates the expression of two slow myosins and their intronic miRNAs, Myh7/miR-208b and Myh7b/miR-499, respectively. miR-208b and miR-499 play redundant roles in the specification of muscle fiber identity by activating slow and repressing fast myofiber gene programs. ...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: van Rooij E, Quiat D, Johnson BA, Sutherland LB, Qi X, Richardson JA, Kelm RJ, Olson EN Tags: Dev Cell Source Type: journals

Moz and Retinoic Acid Coordinately Regulate H3K9 Acetylation, Hox Gene Expression, and Segment Identity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries. PMID: 19922872 [PubMed - as supplied by publisher] (Source: Developmental Cell)
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Voss AK, Collin C, Dixon MP, Thomas T Tags: Dev Cell Source Type: journals

ADAMTS Metalloproteases Generate Active Versican Fragments that Regulate Interdigital Web Regression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We show that combinatorial mouse alleles for the secreted metalloproteases Adamts5, Adamts20 (bt), and Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in Adamts5(-/-);bt/bt mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either Vcan or Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in bt mice, suggesting that cleaved versican was essential for web ...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: McCulloch DR, Nelson CM, Dixon LJ, Silver DL, Wylie JD, Lindner V, Sasaki T, Cooley MA, Argraves WS, Apte SS Tags: Dev Cell Source Type: journals

A FAM21-Containing WASH Complex Regulates Retromer-Dependent Sorting.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Arp2/3 complex regulates endocytosis, sorting, and trafficking, yet the Arp2/3-stimulating factors orchestrating these distinct events remain ill defined. WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) is an Arp2/3 activator with unknown function that was duplicated during primate evolution. We demonstrate that WASH associates with tubulin and localizes to early endosomal subdomains, which are enriched in Arp2/3, F-actin, and retromer components. Although WASH localized with activated receptors, it was not essential for endocytosis. However, WASH did regulate retromer-mediated retrograde CI-MPR traffickin...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Gomez TS, Billadeau DD Tags: Dev Cell Source Type: journals

The Arp2/3 Activator WASH Controls the Fission of Endosomes through a Large Multiprotein Complex.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Arp2/3 complex generates branched actin networks when activated by Nucleation Promoting Factors (NPFs). Recently, the WASH family of NPFs has been identified, but its cellular role is unclear. Here, we show that WASH generates an actin network on a restricted domain of sorting and recycling endosomes. We found that WASH belongs to a multiprotein complex containing seven subunits, including the heterodimer of capping protein (CP). In vitro, the purified WASH complex activates Arp2/3-mediated actin nucleation and binds directly to liposomes. WASH also interacts with dynamin. WASH depletion gives rise to long membrane...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Derivery E, Sousa C, Gautier JJ, Lombard B, Loew D, Gautreau A Tags: Dev Cell Source Type: journals

SUMO Regulates the Assembly and Function of a Cytoplasmic Intermediate Filament Protein in C. elegans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sumoylation is a reversible posttranslational modification that plays roles in many processes, including transcriptional regulation, cell division, chromosome integrity, and DNA damage response. Using a proteomics approach, we identified approximately 250 candidate targets of sumoylation in C. elegans. One such target is the cytoplasmic intermediate filament (cIF) protein named IFB-1, which is expressed in hemidesmosome-like structures in the worm epidermis and is essential for embryonic elongation and maintenance of muscle attachment to the cuticle. In the absence of SUMO, IFB-1 formed ectopic filaments and protein ag...
Source: Developmental Cell - November 17, 2009 Category: Cytology Authors: Kaminsky R, Denison C, Bening-Abu-Shach U, Chisholm AD, Gygi SP, Broday L Tags: Dev Cell Source Type: journals

Myosin II Dynamics Are Regulated by Tension in Intercalating Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Axis elongation in Drosophila occurs through polarized cell rearrangements driven by actomyosin contractility. Myosin II promotes neighbor exchange through the contraction of single cell boundaries, while the contraction of myosin II structures spanning multiple pairs of cells leads to rosette formation. Here we show that multicellular actomyosin cables form at a higher frequency than expected by chance, indicating that cable assembly is an active process. Multicellular cables are sites of increased mechanical tension as measured by laser ablation. Fluorescence recovery after photobleaching experiments show that myosin...
Source: Developmental Cell - October 28, 2009 Category: Cytology Authors: Fernandez-Gonzalez R, Simoes SD, Röper JC, Eaton S, Zallen JA Tags: Dev Cell Source Type: journals

A Yeast Killer Toxin Screen Provides Insights into A/B Toxin Entry, Trafficking, and Killing Mechanisms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Like Ricin, Shiga, and Cholera toxins, yeast K28 is an A/B toxin that depends on endocytosis and retrograde trafficking for toxicity. Knowledge of the specific proteins, lipids, and mechanisms required for trafficking and killing by these toxins remains incomplete. Since K28 is a model for clinically relevant toxins, we screened over 5000 yeast mutants, identifying 365 that affect K28 sensitivity. Hypersensitive mutants revealed cytoprotective pathways, including stress-activated signaling and protein degradation. Resistant mutants clustered to endocytic, lipid organization, and cell wall biogenesis pathways. Furthermo...
Source: Developmental Cell - October 20, 2009 Category: Cytology Authors: Carroll SY, Stirling PC, Stimpson HE, Gießelmann E, Schmitt MJ, Drubin DG Tags: Dev Cell Source Type: journals

More than a pipe dream: uncovering mechanisms of vascular lumen formation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An unresolved question in vasculogenesis is how mammalian endothelial cells make lumens in developing vessels. In this issue of Developmental Cell, Strilic et al. present a comprehensive analysis of murine arterial lumen formation that defines cellular and molecular events required for lumen morphogenesis and argues against a previous paradigm of lumen formation. PMID: 19853555 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Nelson KS, Beitel GJ Tags: Dev Cell Source Type: journals

Microtubule length control, a team sport?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Kinesin-8 family members function in microtubule length control and exhibit highly processive plus-end directed motility in conjunction with microtubule dissassembly activity. In a recent issue of Cell, Varga and colleagues describe how these two activities may be used to simultaneously measure and adjust the length of cellular microtubules. PMID: 19853556 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Wordeman L, Stumpff J Tags: Dev Cell Source Type: journals

More than patterning-hox genes and the control of posterior axial elongation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hox genes are well known for their evolutionarily conserved role in patterning the body axis. Now, Young et al. in this issue of Developmental Cell present evidence that at least in mouse embryos Hox genes do more, namely controlling the process of axis formation itself. PMID: 19853557 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Aulehla A, Pourquie O Tags: Dev Cell Source Type: journals

About combs, notches, and tumors: epigenetics meets signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The identities of cells, determined by differential gene expression, are heritably maintained by the antagonistic functions of Polycomb group (PcG) and Trithorax group proteins. Two recent papers shed new light on tumor suppressive functions of PcG by reporting direct silencing of the Notch and JAK/STAT signaling pathways in Drosophila melanogaster. PMID: 19853558 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Merdes G, Paro R Tags: Dev Cell Source Type: journals

Arrestin Development: Emerging Roles for beta-arrestins in Developmental Signaling Pathways.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Arrestins were identified as mediators of G protein-coupled receptor (GPCR) desensitization and endocytosis. However, it is now clear that they scaffold many intracellular signaling networks to modulate the strength and duration of signaling by diverse types of receptors-including those relevant to the Hedgehog, Wnt, Notch, and TGFbeta pathways-and downstream kinases such as the MAPK and Akt/PI3K cascades. The involvement of arrestins in many discrete developmental signaling events suggests an indispensable role for these multifaceted molecular scaffolds. PMID: 19853559 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Kovacs JJ, Hara MR, Davenport CL, Kim J, Lefkowitz RJ Tags: Dev Cell Source Type: journals

A Role for C. elegans Eph RTK Signaling in PTEN Regulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PTEN is one of the most commonly lost tumor suppressors in human cancer and is known to inhibit insulin signaling. Eph receptor tyrosine kinases (RTKs) have also been implicated in cancer formation and progression, and they have diverse functions, including nervous and vascular system development. We show that in C. elegans, the VAB-1 Eph kinase domain physically interacts with and phosphorylates PTEN (DAF-18), diminishing its protein levels and function. vab-1 mutants show increased longevity and sensitivity to dauer conditions, consistent with increased DAF-18/PTEN activity and decreased insulin-like signaling. Moreo...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Brisbin S, Liu J, Boudreau J, Peng J, Evangelista M, Chin-Sang I Tags: Dev Cell Source Type: journals

The core protein of glypican dally-like determines its biphasic activity in wingless morphogen signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dally-like (Dlp) is a glypican-type heparan sulfate proteoglycan (HSPG), containing a protein core and attached glycosaminoglycan (GAG) chains. In Drosophila wing discs, Dlp represses short-range Wingless (Wg) signaling, but activates long-range Wg signaling. Here, we show that Dlp core protein has similar biphasic activity as wild-type Dlp. Dlp core protein can interact with Wg; the GAG chains enhance this interaction. Importantly, we find that Dlp exhibits a biphasic response, regardless of whether its glycosylphosphatidylinositol linkage to the membrane can be cleaved. Rather, the transition from signaling activator...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Yan D, Wu Y, Feng Y, Lin SC, Lin X Tags: Dev Cell Source Type: journals

MT2-MMP-Dependent Release of Collagen IV NC1 Domains Regulates Submandibular Gland Branching Morphogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here, we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Specifically, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tis...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Rebustini IT, Myers C, Lassiter KS, Surmak A, Szabova L, Holmbeck K, Pedchenko V, Hudson BG, Hoffman MP Tags: Dev Cell Source Type: journals

Latrophilin Signaling Links Anterior-Posterior Tissue Polarity and Oriented Cell Divisions in the C. elegans Embryo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Understanding the mechanisms that coordinate the orientation of cell division planes during embryogenesis and morphogenesis is a fundamental problem in developmental biology. Here we show that the orphan receptor lat-1, a homolog of vertebrate latrophilins, plays an essential role in the establishment of tissue polarity in the C. elegans embryo. We provide evidence that lat-1 is required for the alignment of cell division planes to the anterior-posterior axis and acts in parallel to known polarity and morphogenesis signals. lat-1 is a member of the Adhesion-GPCR protein family and is structurally related to flamingo/CE...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Langenhan T, Prömel S, Mestek L, Esmaeili B, Waller-Evans H, Hennig C, Kohara Y, Avery L, Vakonakis I, Schnabel R, Russ AP Tags: Dev Cell Source Type: journals

The molecular basis of vascular lumen formation in the developing mouse aorta.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In vertebrates, endothelial cells (ECs) form blood vessels in every tissue. Here, we investigated vascular lumen formation in the developing aorta, the first and largest arterial blood vessel in all vertebrates. Comprehensive imaging, pharmacological manipulation, and genetic approaches reveal that, in mouse embryos, the aortic lumen develops extracellularly between adjacent ECs. We show that ECs adhere to each other, and that CD34-sialomucins, Moesin, F-actin, and non-muscle Myosin II localize at the endothelial cell-cell contact to define the luminal cell surface. Resultant changes in EC shape lead to lumen formation...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Strilić B, Kucera T, Eglinger J, Hughes MR, McNagny KM, Tsukita S, Dejana E, Ferrara N, Lammert E Tags: Dev Cell Source Type: journals

Cdx and hox genes differentially regulate posterior axial growth in Mammalian embryos.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hox and Cdx transcription factors regulate embryonic positional identities. Cdx mutant mice display posterior body truncations of the axial skeleton, neuraxis, and caudal urorectal structures. We show that trunk Hox genes stimulate axial extension, as they can largely rescue these Cdx mutant phenotypes. Conversely, posterior (paralog group 13) Hox genes can prematurely arrest posterior axial growth when precociously expressed. Our data suggest that the transition from trunk to tail Hox gene expression successively regulates the construction and termination of axial structures in the mouse embryo. Thus, Hox genes seem t...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Young T, Rowland JE, van de Ven C, Bialecka M, Novoa A, Carapuco M, van Nes J, de Graaff W, Duluc I, Freund JN, Beck F, Mallo M, Deschamps J Tags: Dev Cell Source Type: journals

LRF Is an Essential Downstream Target of GATA1 in Erythroid Development and Regulates BIM-Dependent Apoptosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
GATA-1-dependent transcription is essential for erythroid differentiation and maturation. Suppression of programmed cell death is also thought to be critical for this process; however, the link between these two features of erythropoiesis has remained elusive. Here, we show that the POZ-Krüppel family transcription factor, LRF (also known as Zbtb7a/Pokemon), is a direct target of GATA1 and plays an essential antiapoptotic role during terminal erythroid differentiation. We find that loss of Lrf leads to lethal anemia in embryos, due to increased apoptosis of late-stage erythroblasts. This programmed cell death is A...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Maeda T, Ito K, Merghoub T, Poliseno L, Hobbs RM, Wang G, Dong L, Maeda M, Dore LC, Zelent A, Luzzatto L, Teruya-Feldstein J, Weiss MJ, Pandolfi PP Tags: Dev Cell Source Type: journals

DNA damage checkpoint maintains CDH1 in an active state to inhibit anaphase progression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
DNA damage checkpoint prevents segregation of damaged chromosomes by imposing cell-cycle arrest. In budding yeast, Mec1, Chk1, and Rad53 (homologous to human ATM/ATR, Chk1, and Chk2 kinases, respectively) are among the main effectors of this pathway. The DNA damage checkpoint is thought to inhibit chromosome segregation by preventing separase-mediated cleavage of cohesins. Here, we describe a regulatory network that prevents segregation of damaged chromosomes by restricting spindle elongation and acts in parallel with inhibition of cohesin cleavage. This control circuit involves Rad53, polo kinase, the anaphase-promoti...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Zhang T, Nirantar S, Lim HH, Sinha I, Surana U Tags: Dev Cell Source Type: journals

Meis Cofactors Control HDAC and CBP Accessibility at Hox-Regulated Promoters during Zebrafish Embryogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. According...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Choe SK, Lu P, Nakamura M, Lee J, Sagerström CG Tags: Dev Cell Source Type: journals

Motif-Blind, Genome-Wide Discovery of cis-Regulatory Modules in Drosophila and Mouse.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present new approaches to cis-regulatory module (CRM) discovery in the common scenario where relevant transcription factors and/or motifs are unknown. Beginning with a small list of CRMs mediating a common gene expression pattern, we search genome-wide for CRMs with similar functionality, using new statistical scores and without requiring known motifs or accurate motif discovery. We cross-validate our predictions on 31 regulatory networks in Drosophila and through correlations with gene expression data. Five predicted modules tested using an in vivo reporter gene assay all show tissue-specific regulatory activity. We al...
Source: Developmental Cell - October 1, 2009 Category: Cytology Authors: Kantorovitz MR, Kazemian M, Kinston S, Miranda-Saavedra D, Zhu Q, Robinson GE, Göttgens B, Halfon MS, Sinha S Tags: Dev Cell Source Type: journals

The curious case of bivalent marks.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bivalently marked chromatin, containing both histone H3 lysine 4 (H3K4) and H3K27 trimethylation, is a hallmark of developmentally regulated paused promoters in mammalian embryonic stem cells. In this issue of Developmental Cell, Akkers et al. report that Xenopus tropicalis embryos transition through early development without the requirement for bivalently marked promoters. PMID: 19758552 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Herz HM, Nakanishi S, Shilatifard A Tags: Dev Cell Source Type: journals

Shugoshin and PP2A: collaborating to keep chromosomes connected.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Timely release of sister chromatid cohesion is essential for accurate chromosome segregation during cell division. Shugoshin forms a complex with the phosphatase PP2A that has been proposed to dephosphorylate cohesin proteins to prevent premature loss of centromeric cohesion. A recent study in Molecular Cell by Xu et al. presents the structure of Shugoshin bound to PP2A and provides evidence that this interaction is required for cohesion protection. PMID: 19758553 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Kateneva AV, Higgins JM Tags: Dev Cell Source Type: journals

Orchestrating twosome and foursome chromosome parties.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The conserved centromere protein C (CENP-C) is indispensable for kinetochore function. Yet its mechanism of action has remained elusive. In this issue of Developmental Cell, Tanaka et al. report that the fission yeast homolog, Cnp3, acts as a linker protein that fulfills a variety of different roles in the bi- and mono-orientation of chromosomes during mitosis and meiosis I. PMID: 19758554 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Kalitsis P, Choo KH Tags: Dev Cell Source Type: journals

Mechanisms of cellular protrusions branch out.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
F-BAR domains bind curved membranes and induce membrane invagination. In a recent Cell paper, Guerrier et al. describe an "inverse" F-BAR family member that induces outward curvature and filopodia in migrating neurons. These findings suggest that F-BAR domains are functionally diverse and regulate different types of membrane morphology. PMID: 19758555 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Carlson B, Soderling SH Tags: Dev Cell Source Type: journals

Actin dynamics at the leading edge: from simple machinery to complex networks.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cell migration is an essential feature of eukaryotic life, required for processes ranging from feeding and phagoctyosis to development, healing, and immunity. Migration requires the actin cytoskeleton, specifically the localized polymerization of actin filaments underneath the plasma membrane. Here we summarize recent developments in actin biology that particularly affect structures at the leading edge of the cell, including the structure of actin branches, the multiple pathways that lead to cytoskeleton assembly and disassembly, and the role of blebs. Future progress depends on connecting these processes and component...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Insall RH, Machesky LM Tags: Dev Cell Source Type: journals

CLIP-170-dependent capture of membrane organelles by microtubules initiates minus-end directed transport.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cytoplasmic microtubules (MTs) continuously grow and shorten at free plus ends. During mitosis, this dynamic behavior allows MTs to capture chromosomes to initiate their movement to the spindle poles; however, the role of MT dynamics in capturing organelles for transport in interphase cells has not been demonstrated. Here we use Xenopus melanophores to test the hypothesis that MT dynamics significantly contribute to the efficiency of MT minus-end directed transport of membrane organelles. We demonstrate that initiation of transport of membrane-bounded melanosomes (pigment granules) to the cell center involves their cap...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Lomakin AJ, Semenova I, Zaliapin I, Kraikivski P, Nadezhdina E, Slepchenko BM, Akhmanova A, Rodionov V Tags: Dev Cell Source Type: journals

CENP-C functions as a scaffold for effectors with essential kinetochore functions in mitosis and meiosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The conserved kinetochore protein CENP-C plays a fundamental role in chromosome segregation, but its specific functions remain elusive. We have gained insights into the role of CENP-C through identification of interacting effector proteins required for kinetochore function in fission yeast. Fta1/CENP-L is a primary effector that associates directly with Cnp3/CENP-C, and ectopic localization of Fta1 largely suppresses the mitotic kinetochore defects of cnp3Delta cells. Pcs1 functions downstream of Cnp3 to prevent merotelic attachment. In meiosis, Cnp3 further associates with and recruits Moa1, a meiosis-specific protein...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Tanaka K, Chang HL, Kagami A, Watanabe Y Tags: Dev Cell Source Type: journals

Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It has been proposed that separase-dependent centriole disengagement at anaphase licenses centrosomes for duplication in the next cell cycle. Here we test whether such a mechanism exists in intact human cells. Loss of separase blocked centriole disengagement during mitotic exit and delayed assembly of new centrioles during the following S phase; however, most engagements were eventually dissolved. We identified Polo-like kinase 1 (Plk1) as a parallel activator of centriole disengagement. Timed inhibition of Plk1 mapped its critical period of action to late G2 or early M phase, i.e., prior to securin destruction and sep...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Tsou MF, Wang WJ, George KA, Uryu K, Stearns T, Jallepalli PV Tags: Dev Cell Source Type: journals

Translational repression of cyclin E prevents precocious mitosis and embryonic gene activation during C. elegans meiosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe a mechanism that prevents precocious mitosis in germ cells undergoing meiosis, propose that this mechanism maintains germ cell identity by delaying the onset of embryonic gene activation until after fertilization, and provide a paradigm for the possible origin of human teratomas. PMID: 19758560 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Biedermann B, Wright J, Senften M, Kalchhauser I, Sarathy G, Lee MH, Ciosk R Tags: Dev Cell Source Type: journals

Redefining the progression of lineage segregations during mammalian embryogenesis by clonal analysis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Clonal lineage information is fundamental in revealing cell fate choices. Using genetic single-cell labeling in utero, we investigated lineage segregations during anteroposterior axis formation in mouse. We show that while endoderm and surface ectoderm segregate during gastrulation, neural ectoderm and mesoderm share a common progenitor persisting through all stages of axis elongation. These data challenge the paradigm that the three germ layers, formed by gastrulation, constitute the primary branchpoints in differentiation of the pluripotent epiblast toward tissue-specific precursors. Bipotent neuromesodermal progenit...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Tzouanacou E, Wegener A, Wymeersch FJ, Wilson V, Nicolas JF Tags: Dev Cell Source Type: journals

Local guidance of emerging vessel sprouts requires soluble Flt-1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Blood vessel networks form via sprouting of endothelial cells from parent vessels. Extrinsic cues guide sprouts after they leave the initiation site, but these cues are likely insufficient to regulate initial outward movement, and many embryonic vessel networks form in the absence of a strong extrinsic gradient. We hypothesized that nascent sprouts are guided by spatial cues produced along their own vessels, and that soluble Flt-1 (sFlt-1) participates in this guidance. Analysis of developing vessels with perturbed flt-1 function revealed misguided emerging sprouts, and transgenic sFlt-1 rescued sprout guidance paramet...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Chappell JC, Taylor SM, Ferrara N, Bautch VL Tags: Dev Cell Source Type: journals

The vacuolar proton pump, V-ATPase, is required for notch signaling and endosomal trafficking in Drosophila.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have identified Rabconnectin-3alpha and beta (Rbcn-3A and B) as two regulators of Notch signaling in Drosophila. We found that, in addition to disrupting Notch signaling, mutations in Rbcn-3A and B cause defects in endocytic trafficking, where Notch and other membrane proteins accumulate in late endosomal compartments. We show that Notch is transported to the surface of mutant cells and that signaling is disrupted after the S2 cleavage. Interestingly, the yeast homolog of Rbcn-3A, Rav1, regulates the V-ATPase proton pump responsible for acidifying intracellular organelles. We found that, similarly, Rbcn-3A and B app...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Yan Y, Denef N, Schüpbach T Tags: Dev Cell Source Type: journals

A link between ER tethering and COP-I vesicle uncoating.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The yeast Dsl1p vesicle tethering complex, comprising the three subunits Dsl1p, Dsl3p, and Tip20p, is stably associated with three endoplasmic reticulum-localized Q-SNAREs and is believed to play a central role in the tethering and fusion of Golgi-derived COP-I transport vesicles. Dsl1p also interacts directly with COP-I subunits. We now show that binding of Dsl1p to COP-I subunits involves binding sites identical to those involved in interactions between COP-I subunits that stabilize the COP-I coat. Cells with defects in Dsl/SNARE complex function show massive accumulation of COP-I-coated vesicles in a cluster to whic...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Zink S, Wenzel D, Wurm CA, Schmitt HD Tags: Dev Cell Source Type: journals

Drosophila maelstrom ensures proper germline stem cell lineage differentiation by repressing microRNA-7.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nuage is a germline-unique perinuclear structure conserved throughout the animal kingdom. Maelstrom (Mael) is an unusual nuage component, as it is also found in the nucleus. Mael contains a High Mobility Group box, known to mediate DNA binding. We show that Mael nuclear function is required for proper differentiation in the Drosophila germline stem cell (GSC) lineage. In mael mutant testes, transit-amplifying cysts fail to differentiate into primary spermatocytes, instead breaking down into ectopic GSCs and smaller cysts, due to a depletion of Bag-of-marbles (Bam) protein. Mael regulates Bam via repression of miR-7. Ma...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Pek JW, Lim AK, Kai T Tags: Dev Cell Source Type: journals

A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Epigenetic mechanisms set apart the active and inactive regions in the genome of multicellular organisms to produce distinct cell fates during embryogenesis. Here, we report on the epigenetic and transcriptome genome-wide maps of gastrula-stage Xenopus tropicalis embryos using massive parallel sequencing of cDNA (RNA-seq) and DNA obtained by chromatin immunoprecipitation (ChIP-seq) of histone H3 K4 and K27 trimethylation and RNA Polymerase II (RNAPII). These maps identify promoters and transcribed regions. Strikingly, genomic regions featuring opposing histone modifications are mostly transcribed, reflecting spatially ...
Source: Developmental Cell - August 31, 2009 Category: Cytology Authors: Akkers RC, van Heeringen SJ, Jacobi UG, Janssen-Megens EM, Françoijs KJ, Stunnenberg HG, Veenstra GJ Tags: Dev Cell Source Type: journals

Breaking the silence: stimulating proliferation of adult cardiomyocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Several recent findings challenge our view of the heart as a postmitotic organ and suggest that the adult heart has some capacity to regenerate. Bersell et al. in a recent issue of Cell report that neuregulin1-mediated activation of ErbB2/4 receptors induces proliferation of adult mononuclear cardiomyocytes. PMID: 19686672 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - July 31, 2009 Category: Cytology Authors: Braun T, Dimmeler S Tags: Dev Cell Source Type: journals

Notch signaling: linking delta endocytosis and cell polarity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Activation of Notch by its transmembrane ligand Delta requires the E3 ubiquitin ligases Neuralized or Mind bomb and endocytosis of the ubiquitinated ligand. In this issue of Developmental Cell, Ossipova et al. show that the polarity regulator PAR-1 phosphorylates Mind bomb, leading to the degradation of Mind bomb and to changes in cell fate due to loss of Notch signaling. PMID: 19686673 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - July 31, 2009 Category: Cytology Authors: Krahn MP, Wodarz A Tags: Dev Cell Source Type: journals