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Transposable elements in gene regulation and in the evolution of vertebrate genomes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Repetitive DNA and in particular transposable elements have been intimately linked to eukaryotic genomes for millions of years. Once overlooked for being only a collection of selfish debris and a nuisance for sequence assembly, genomic repeats are now being recognized as a key driving force in genome evolution. Indeed, by changing the DNA landscape of genomes, transposable elements have been a rich source of innovation in genes, regulatory elements and genome structures. In this review, I will focus on recent advances that demonstrate that genomic repeats have had a global impact on vertebrate gene regulatory networks....
Source: Current Opinion in Genetics and Development - November 12, 2009 Category: Genetics & Stem Cells Authors: Bourque G Tags: Curr Opin Genet Dev Source Type: journals

Comparative genomics of gene regulation-conservation and divergence of cis-regulatory information.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We recently witnessed a tremendous increase in genomics studies on gene regulation and in entirely sequenced genomes from closely related species. This has triggered analyses that suggest a wide range of evolutionary dynamics of gene regulation, from rapid turnover of transcription-factor binding sites to conservation of enhancer function across large evolutionary distances. Many examples show that enhancers can evolve beyond recognizable sequence similarity while retaining function. However, bioinformatics approaches are increasingly able to detect conserved regulatory elements through characteristic evolutionary sequ...
Source: Current Opinion in Genetics and Development - November 11, 2009 Category: Genetics & Stem Cells Authors: Meireles-Filho AC, Stark A Tags: Curr Opin Genet Dev Source Type: journals

Regulatory DNAs and the evolution of human development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Changes in gene regulation have long been thought to underlie biological differences between humans and other primates. Recent advances have facilitated the study of human-specific sequence changes in regulatory DNAs in the context of human development. Comparative genomic analyses coupled with genome-wide in vivo developmental enhancer screens have identified thousands of known and likely regulatory elements in the genome. These have provided the substrate for statistical and experimental identification of regulatory sequences with human-specific developmental activities. On the basis of these early results, the outli...
Source: Current Opinion in Genetics and Development - November 11, 2009 Category: Genetics & Stem Cells Authors: Noonan JP Tags: Curr Opin Genet Dev Source Type: journals

Network design principles from the sea urchin embryo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
As gene regulatory network models encompass more and more of the specification processes underlying sea urchin embryonic development, topological themes emerge that imply the existence of structural network 'building blocks'. These are subcircuits which perform given logic operations in the spatial control of gene expression. The various parts of the sea urchin gene regulatory networks offer instances of the same subcircuit topologies accomplishing the same developmental logic functions but using different genes. These subcircuits are dedicated to specific developmental functions, unlike simpler 'motifs', and may indic...
Source: Current Opinion in Genetics and Development - November 11, 2009 Category: Genetics & Stem Cells Authors: Davidson EH Tags: Curr Opin Genet Dev Source Type: journals

Evolution of transcriptional control in mammals.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Changes in gene expression directed by transcriptional regulators can give rise to new phenotypes. While gene expression profiles can be maintained across large evolutionary distances, transcription factor-DNA interactions diverge rapidly. The application of new genome-wide methodologies has begun refining our global understanding of when and where mammalian transcription factors interact with DNA, thereby providing new insight into the mechanisms of transcriptional evolution. The interplay between cis and trans regulation of gene expression is an increasingly active area of investigation, and recent studies suggest th...
Source: Current Opinion in Genetics and Development - November 11, 2009 Category: Genetics & Stem Cells Authors: Wilson MD, Odom DT Tags: Curr Opin Genet Dev Source Type: journals

Polyploidy and genome restructuring: a variety of outcomes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dramatic genome rearrangement has been observed after whole genome duplication (WGD) in some plant species, leading many to suggest that genome restructuring may be a common consequence of WGD. However, recent analyses of ancient WGDs in yeast and vertebrates have not shown any evidence for increased rearrangement after WGD. When WGD events across all three kingdoms of eukaryotic life are considered-including plants, yeast, vertebrates, and human cancers-we find that a variety of outcomes are possible, from genome restructuring to genome stasis. In fact, striking differences in genome change after WGD can be observed w...
Source: Current Opinion in Genetics and Development - November 7, 2009 Category: Genetics & Stem Cells Authors: Hufton AL, Panopoulou G Tags: Curr Opin Genet Dev Source Type: journals

Functional and ecological impacts of horizontal gene transfer in eukaryotes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Horizontal gene transfer (HGT) is known to have contributed to the content of eukaryotic genomes, but the direct effects of HGT on eukaryotic evolution are more obscure because many of the best supported cases involve a new gene replacing a functionally similar homologue. Here, several cases of HGT conferring a plausible adaptive advantage are reviewed to examine emerging trends in such transfer events. In particular, HGT seems to play an important role in adaptation to parasitism and pathogenesis, as well as to other specific environmental conditions such as anaerobiosis or nitrogen and iron limitation in marine envir...
Source: Current Opinion in Genetics and Development - November 6, 2009 Category: Genetics & Stem Cells Authors: Keeling PJ Tags: Curr Opin Genet Dev Source Type: journals

Early evolution of metazoan transcription factors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Analyses of recently sequenced sponge, cnidarian, placozoan, and choanoflagellate genomes have revealed that most transcription factor (TF) classes and families expressed during bilaterian development originated at the dawn of the animal kingdom, before the divergence of contemporary animal lineages. The ancestral metazoan genome included members of the bHLH, Mef2, Fox, Sox, T-box, ETS, nuclear receptor, Rel/NF-kappaB, bZIP, and Smad families, and a diversity of homeobox-containing classes, including ANTP, Prd-like, Pax, POU, LIM-HD, Six, and TALE. As many of these TF classes and families appear to be metazoan specific...
Source: Current Opinion in Genetics and Development - October 30, 2009 Category: Genetics & Stem Cells Authors: Degnan BM, Vervoort M, Larroux C, Richards GS Tags: Curr Opin Genet Dev Source Type: journals

The structure-function link of compensated chromatin in Drosophila.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
All the aspects of transcription are controlled by complexes that modify or remodel chromatin at the level of individual genes, gene clusters, or whole chromosomes. The MSL complex that is responsible for dosage compensation in Drosophila is an example of complexes that operate at the whole-chromosome level on the transcription of individual genes. Recent experiments using traditional genetic analysis, molecular cytology, chromatin immunoprecipitation, or microarray technology have characterized the function of the two known enzymatic components of the MSL core complex and have identified the sequence characteristics t...
Source: Current Opinion in Genetics and Development - October 30, 2009 Category: Genetics & Stem Cells Authors: Lucchesi JC Tags: Curr Opin Genet Dev Source Type: journals

From elements to modules: regulatory evolution in Ascomycota fungi.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Regulatory divergence is likely a major driving force in evolution. Comparative transcriptomics provides a new glimpse into the evolution of gene regulation. Ascomycota fungi are uniquely suited among eukaryotes for studies of regulatory evolution, because of broad phylogenetic scope, many sequenced genomes, and facility of genomic analysis. Here we review the substantial divergence in gene expression in Ascomycota and how this is reconciled with the modular organization of transcriptional networks. We show that flexibility and redundancy in both cis-regulation and trans-regulation can lead to changes from altered expr...
Source: Current Opinion in Genetics and Development - October 28, 2009 Category: Genetics & Stem Cells Authors: Wohlbach DJ, Thompson DA, Gasch AP, Regev A Tags: Curr Opin Genet Dev Source Type: journals

Molecular genetics of tooth development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Organogenesis depends upon a well-ordered series of inductive events involving coordination of molecular pathways that regulate the generation and patterning of specific cell types. Key questions in organogenesis involve the identification of the molecular mechanisms by which proteins interact to organize distinct pattern formation and cell fate determination. Tooth development is an excellent context for investigating this complex problem because of the wealth of information emerging from studies of model organisms and human mutations. Since there are no obvious sources of stem cells in adult human teeth, any attempt ...
Source: Current Opinion in Genetics and Development - October 27, 2009 Category: Genetics & Stem Cells Authors: Bei M Tags: Curr Opin Genet Dev Source Type: journals

Vascular morphogenesis: a Wnt for every vessel?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Blood vessel development requires orchestrated activities of heterogeneous endothelial cell (EC) populations to create a hierarchically branched tubular network. Endothelial heterogeneity is manifested in organ-specific endothelial differentiation and function in the mature vasculature. During sprouting angiogenesis, ECs are specified by Dll4/Notch signalling into leading tip cells and following stalk cells, which together through coordinated migration and proliferation shape the nascent vascular sprout. Wnt-signalling influences many aspects of branching tubulogenesis in various species and organ systems, often in coo...
Source: Current Opinion in Genetics and Development - October 26, 2009 Category: Genetics & Stem Cells Authors: Franco CA, Liebner S, Gerhardt H Tags: Curr Opin Genet Dev Source Type: journals

Finding distal regulatory elements in the human genome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transcriptional regulation of human genes depends not only on promoters and nearby cis-regulatory elements, but also on distal regulatory elements such as enhancers, insulators, locus control regions, and silencing elements, which are often located far away from the genes they control. Our knowledge of human distal regulatory elements is very limited, but the last several years have seen rapid progress in the development of strategies to identify these long-range regulatory sequences throughout the human genome. Here, we review these advances, focusing on two important classes of distal regulatory sequences-enhancers a...
Source: Current Opinion in Genetics and Development - October 23, 2009 Category: Genetics & Stem Cells Authors: Heintzman ND, Ren B Tags: Curr Opin Genet Dev Source Type: journals

Nuclear organization in the 3D space of the nucleus-cause or consequence?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent evidence suggests that dynamic three-dimensional genomic interactions in the nucleus exert critical roles in regulated gene expression. Here, we review a series of recent paradigm-shifting experiments that highlight the existence of specific gene networks within the self-organizing space of the nucleus. These gene networks, evidenced by long-range intrachromosomal and interchromosomal interactions, can be considered as the cause or consequence of regulatory biological programs. Changes in nuclear architecture are a hallmark of laminopathies and likely potentiate genome rearrangements critical for tumor progressi...
Source: Current Opinion in Genetics and Development - October 18, 2009 Category: Genetics & Stem Cells Authors: Nunez E, Fu XD, Rosenfeld MG Tags: Curr Opin Genet Dev Source Type: journals

From cells to organs: new insight into organ morphogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19836943 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - October 14, 2009 Category: Genetics & Stem Cells Authors: Affolter M, Zeller R Tags: Curr Opin Genet Dev Source Type: journals

Transcriptional networks controlling skeletal development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The formation of the vertebrate skeletal elements relies on the differentiation of the required cell types, chondrocytes and osteoblasts, which are derived from a common mesenchymal precursor. Furthermore it requires coordination between maturation of chondrocytes and osteoblasts to enable proper growth and development of skeletal elements. Over the past years various transcription factors have been identified on the basis of in vivo and in vitro studies that play important roles for skeletal formation being either active in chondrocytes or osteoblasts or even in both cell types. In this article their mode of action in...
Source: Current Opinion in Genetics and Development - October 13, 2009 Category: Genetics & Stem Cells Authors: Hartmann C Tags: Curr Opin Genet Dev Source Type: journals

Kidney development: from ureteric bud formation to branching morphogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Epithelial branching morphogenesis is critical to the formation of various organs such as the vasculature, mammary glands, lungs, and kidneys in vertebrate embryos. One fascinating aspect of branching morphogenesis is to understand how a simple epithelial tube grows by reiterative branching to form a complex epithelial tree structure. Recent studies combining mouse genetics and chimeric analysis with live imaging have uncovered the molecular networks and interactions that govern kidney branching morphogenesis. This review focuses on ureteric bud (UB) formation and epithelial branching during kidney development. The inv...
Source: Current Opinion in Genetics and Development - October 11, 2009 Category: Genetics & Stem Cells Authors: Michos O Tags: Curr Opin Genet Dev Source Type: journals

Shaping the vertebrate eye.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
For over a century, the vertebrate eye has served as a paradigm for organogenesis. It forms through a complex sequence of morphogenetic events, involving the lateral evagination of the optic vesicles and their subsequent folding into the optic cups. Through intensive studies by experimental embryologists, anatomical descriptions of the process were available since many decades. Recent genetic and molecular work has illuminated essential features of the stereotyped cellular behaviour driving eye morphogenesis. The first pieces of the molecular machinery operating in each individual progenitor cell have been identified. ...
Source: Current Opinion in Genetics and Development - October 7, 2009 Category: Genetics & Stem Cells Authors: Martinez-Morales JR, Wittbrodt J Tags: Curr Opin Genet Dev Source Type: journals

Balancing dormant and self-renewing hematopoietic stem cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The mouse hematopoietic stem cell (HSC) is probably the best-understood somatic stem cell in higher organisms. Recent studies have shown that the highest self-renewal potential is most likely contained within an exceedingly small number of deeply dormant bone marrow HSCs. These stem cells are housed in individual niches that preserve their dormancy via signaling molecules such as Thrombopoietin, Angiopoietins, and Stem Cell Factor. In response to injury cues, dormant HSCs are efficiently activated and produce numerous progenitors and mature cells. A series of intracellular regulatory molecules including FoxOs, mTORC1, ...
Source: Current Opinion in Genetics and Development - October 4, 2009 Category: Genetics & Stem Cells Authors: Wilson A, Laurenti E, Trumpp A Tags: Curr Opin Genet Dev Source Type: journals

Bringing together components of the fly renal system.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The function of all animal excretory systems is to rid the body of toxins and to maintain homeostatic balance. Although excretory organs in diverse animal species appear superficially different they are often built on two common principals: filtration and tubular secretion/reabsorbtion. The Drosophila excretory system is composed of filtration nephrocytes and Malpighian (renal) tubules. Here we review recent molecular genetic data on the development and differentiation of nephrocytes and renal tubules. We focus in particular on the molecular mechanisms that underpin key cell and tissue behaviours during morphogenesis, ...
Source: Current Opinion in Genetics and Development - September 24, 2009 Category: Genetics & Stem Cells Authors: Denholm B, Skaer H Tags: Curr Opin Genet Dev Source Type: journals

New horizons at the caudal embryos: coordinated urogenital/reproductive organ formation by growth factor signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cloaca/urogenital sinus and its adjacent region differentiate into the urogenital/reproductive organs. Caudal regression syndrome (CRS; including mermaid syndrome), a type of severe cloacal malformation displays hindlimb fusion and urogenital organ defects, thus suggesting that such defects are caused by several morphogenetic alterations during early development. The attenuation of bone morphogenetic protein (Bmp) signaling at the posterior primitive streak of embryos leads to the caudal dysmorphogenesis including the cloaca and fusion of both hindlimbs. Genetic tissue lineage studies indicate the presence of coord...
Source: Current Opinion in Genetics and Development - September 15, 2009 Category: Genetics & Stem Cells Authors: Suzuki K, Economides A, Yanagita M, Graf D, Yamada G Tags: Curr Opin Genet Dev Source Type: journals

Distinct and dynamic myogenic populations in the vertebrate embryo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Myogenic cells in the body of vertebrates derive from the dorsal somite, the dermomyotome, where multipotent cells are present. Regulation of cell fate choice is discussed, as is that of progenitor cell self-renewal once cells have entered the myogenic programme. Ongoing research on the formation of the first skeletal muscle, the myotome, is presented with emphasis on mechanisms controlling the early segregation of slow and fast muscle lineages that characterizes this process in the zebrafish embryo. Further insights into myogenic populations that contribute to trunk and limb development at different stages are summari...
Source: Current Opinion in Genetics and Development - September 14, 2009 Category: Genetics & Stem Cells Authors: Buckingham M, Vincent SD Tags: Curr Opin Genet Dev Source Type: journals

Stage- and area-specific control of stem cells in the developing nervous system.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The spatiotemporal control of proliferation and differentiation in neural stem cells (NSCs) is essential to produce a functional nervous system (NS). Stem cells in different areas and at different time points during development have to produce different types of cells in a precise manner. Recent studies uncovered a plethora of cell extrinsic as well as intrinsic factors that play crucial roles in the area-specific and stage-specific control of NSCs. Moreover, recapitulation of the spatiotemporal specification of NSCs in vitro opens new avenues for future applications. In this review, we have selected some key molecules...
Source: Current Opinion in Genetics and Development - September 9, 2009 Category: Genetics & Stem Cells Authors: Falk S, Sommer L Tags: Curr Opin Genet Dev Source Type: journals

Building limb morphology through integration of signalling modules.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Growth and patterning of the vertebrate limb relies on signals produced by three discrete signalling centres: the Apical Ectodermal Ridge (AER), the Zone of Polarising Activity (ZPA) and the dorsal ectoderm. The molecular identities of these signals and their associated downstream pathways have begun to be uncovered. In this review, we focus on recent work that has highlighted the importance of cross-talk between these signalling centres and how mesenchymal progenitors integrate multiple signalling inputs. We also discuss recent evidence suggesting how modulations of key signalling pathways have been used to generate t...
Source: Current Opinion in Genetics and Development - August 31, 2009 Category: Genetics & Stem Cells Authors: Duboc V, Logan MP Tags: Curr Opin Genet Dev Source Type: journals

The fabulous destiny of the Drosophila heart.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
For the last 15 years the fly cardiovascular system has attracted developmental geneticists for its potential as a model system of organogenesis. Heart development in Drosophila indeed provides a remarkable system for elucidating the basic molecular and cellular mechanisms of morphogenesis and, more recently, for understanding the genetic control of cardiac physiology. The success of these studies can in part be attributed to multidisciplinary approaches, the multiplicity of existing genetic tools, and a detailed knowledge of the system. Striking similarities with vertebrate cardiogenesis have long been stressed, in pa...
Source: Current Opinion in Genetics and Development - August 27, 2009 Category: Genetics & Stem Cells Authors: Medioni C, Sénatore S, Salmand PA, Lalevée N, Perrin L, Sémériva M Tags: Curr Opin Genet Dev Source Type: journals

The pancreatic beta-cell in the islet and organ community.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The endocrine pancreas consists of highly vascularized and innervated endocrine mini-organs-the islets of Langerhans. These contain multiple types of hormone-producing cells, including the insulin-secreting beta-cell. The major task of the fully differentiated beta-cell is the tight regulation of blood glucose levels by secreting insulin into the blood stream. This requires molecular features to measure glucose and produce, process, and release insulin by exocytosis. Now multiple interactions with endocrine and nonendocrine islet cells as well as with other organs have been shown to affect the developing as well as the...
Source: Current Opinion in Genetics and Development - August 24, 2009 Category: Genetics & Stem Cells Authors: Eberhard D, Lammert E Tags: Curr Opin Genet Dev Source Type: journals

Small RNAs and developmental timing in plants.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
MicroRNAs (miRNAs) were originally discovered as regulators of developmental timing in C. elegans. Recent results have revealed that miRNAs also regulate developmental timing in plants, and have provided a long-awaited molecular connection between the juvenile-to-adult transition and flowering. Specifically, the transition from juvenile to adult development in flowering plants is regulated by two temporally expressed miRNAs, miR156 and miR172. These miRNAs target two families of plant-specific transcription factors (respectively, SBP-box and AP2-like factors) that cooperate to regulate phase-specific vegetative traits,...
Source: Current Opinion in Genetics and Development - July 31, 2009 Category: Genetics & Stem Cells Authors: Poethig RS Tags: Curr Opin Genet Dev Source Type: journals

Developmental biology moves forward in the 21st century.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19647991 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - July 30, 2009 Category: Genetics & Stem Cells Authors: Anderson K, Irvine K Tags: Curr Opin Genet Dev Source Type: journals

Regulation of cell migration during chick gastrulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Gastrulation in chick starts with large-scale cell flows in the epiblast and hypoblast, which transport the mesendoderm into the midline of the embryo to form the primitive streak. Several mechanisms such as cell-cell intercalation, deformations of the extracellular matrix and directed cell movements in response to chemical gradients have been proposed to play a role in streak formation. In the streak the epiblast cells undergo an epithelial to mesenchymal transition (EMT), which involves the breakdown of apical junctions and changes in RhoA-dependent signalling to integrins that mediated contact with the basal lamina....
Source: Current Opinion in Genetics and Development - July 29, 2009 Category: Genetics & Stem Cells Authors: Chuai M, Weijer CJ Tags: Curr Opin Genet Dev Source Type: journals

Running the gauntlet: an overview of the modalities of travel employed by the putative morphogen Nodal.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A fundamental challenge in biology is to explain how progenitor cells in developing tissues acquire distinct fates according to their position. In vertebrates, the positional information that specifies the germ layers and the primary body axes is mediated by Nodal. Nodal meets the criteria of a morphogen since it can diffuse through tissues and signal far away from its source to directly specify multiple cell fates in a dosage-dependent manner. To consider the relationship between trafficking and graded Nodal signaling, this review summarizes recent findings how the spreading of Nodal activity is regulated by factors t...
Source: Current Opinion in Genetics and Development - July 21, 2009 Category: Genetics & Stem Cells Authors: Constam DB Tags: Curr Opin Genet Dev Source Type: journals

Germ cell specification in mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Specification of germ cell fate is vital to development and heredity. In mice, germ cell fate is induced in a subset of pluripotent epiblast cells during early gastrulation. Reflecting the function of the germ line as the transducer of genetic information, germ cell specification integrates at least three key events: repression of the somatic program, re-acquisition of potential pluripotency, and ensuing genome-wide epigenetic reprogramming. Blimp1 and Prdm14 are the two critical transcriptional regulators that orchestrate these events. The recent clarification of the mechanism by which signaling activities confer the ...
Source: Current Opinion in Genetics and Development - July 15, 2009 Category: Genetics & Stem Cells Authors: Saitou M Tags: Curr Opin Genet Dev Source Type: journals

The role of Notch in patterning the human vertebral column.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The components of the Notch signaling pathway and the mechanics of signal transduction have largely been established in Drosophila. Although essential for many developmental processes in invertebrates and vertebrates, this review focuses on Notch signaling in the vertebrate-specific process of somitogenesis. More specifically it describes that mutations in genes encoding Notch pathway components (DLL3, MESP2, LFNG and HES7) cause severe congenital vertebral defects in humans. Importantly, this review highlights studies demonstrating that Dll3 is unique amongst DSL ligands acting as an inhibitor and not an activator of ...
Source: Current Opinion in Genetics and Development - July 13, 2009 Category: Genetics & Stem Cells Authors: Dunwoodie SL Tags: Curr Opin Genet Dev Source Type: journals

Early zebrafish development: It's in the maternal genes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The earliest stages of embryonic development in all animals examined rely on maternal gene products that are generated during oogenesis and supplied to the egg. The period of maternal control of embryonic development varies among animals according to the onset of zygotic transcription and the persistence of maternal gene products. This maternal regulation has been little studied in vertebrates, owing to the difficulty in manipulating maternal gene function and lack of basic molecular information. However, recent maternal-effect screens in the zebrafish have generated more than 40 unique mutants that are providing new m...
Source: Current Opinion in Genetics and Development - July 13, 2009 Category: Genetics & Stem Cells Authors: Abrams EW, Mullins MC Tags: Curr Opin Genet Dev Source Type: journals

Building the world's best hearing aid; regulation of cell fate in the cochlea.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In mammals, auditory perception is initially mediated through sensory cells located in a rigorously patterned mosaic of unique cell types located within the coiled cochlea. Identification of the factors that direct multipotent progenitor cells to develop as each of these specialized cell types has the potential to enhance our understanding of the development of the auditory system and to identify potential targets for regenerative therapies. Recent results have identified specific signaling molecules and pathways, including Notch, Hedgehog, Sox2 and Fgfs, that guide progenitor cells to develop first as a sensory precur...
Source: Current Opinion in Genetics and Development - July 12, 2009 Category: Genetics & Stem Cells Authors: Puligilla C, Kelley MW Tags: Curr Opin Genet Dev Source Type: journals

FERM proteins in animal morphogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Proteins containing a FERM domain are ubiquitous components of the cytocortex of animal cells where they are engaged in structural, transport, and signaling functions. Recent years have seen a wealth of genetic studies in model organisms that explore FERM protein function in development and tissue organization. In addition, mutations in several FERM protein-encoding genes have been associated with human diseases. This review will provide a brief overview of the FERM domain structure and the FERM protein superfamily and then discuss recent advances in our understanding of the mechanism of function and developmental requ...
Source: Current Opinion in Genetics and Development - July 8, 2009 Category: Genetics & Stem Cells Authors: Tepass U Tags: Curr Opin Genet Dev Source Type: journals

Temporal dynamics of patterning by morphogen gradients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Morphogens act as graded positional cues to control cell fate specification in many developing tissues. This concept, in which a signaling gradient regulates differential gene expression in a concentration-dependent manner, has received considerable experimental support. Nevertheless, several recent studies have challenged the straightforward model of morphogen activity. In particular, the observation that pattern formation is a dynamic process has raised questions about the influence of time on morphogen activity. Here we propose that the spatiotemporal dynamics of the cellular response to a morphogen gradient depend ...
Source: Current Opinion in Genetics and Development - July 8, 2009 Category: Genetics & Stem Cells Authors: Kutejova E, Briscoe J, Kicheva A Tags: Curr Opin Genet Dev Source Type: journals

An expanding job description for Blimp-1/PRDM1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The master transcriptional regulator Blimp-1/PRDM1 contains an N-terminal PR/SET domain and five C2H2 zinc fingers located near its C-terminus that mediate DNA binding, nuclear import and recruitment of histone modifying enzymes. These activities account for its ability to control cell-fate decisions in the embryo and govern tissue homeostasis in multiple cell types in the adult organism. New experiments demonstrate an increasing degree of complexity associated with Blimp-1/PRDM1 target site selection and its associations with epigenetic modifiers. Our current understanding of how this single unique species within the ...
Source: Current Opinion in Genetics and Development - July 7, 2009 Category: Genetics & Stem Cells Authors: Bikoff EK, Morgan MA, Robertson EJ Tags: Curr Opin Genet Dev Source Type: journals

Emerging patterns in planarian regeneration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the past decade, the planarian has become an increasingly tractable invertebrate model for the investigation of regeneration and stem cell biology. Application of a variety of techniques and development of genomic reagents in this system have enabled exploration of the molecular mechanisms by which pluripotent somatic stem cells called neoblasts replenish, repair, and regenerate planarian tissues and organs. Recent investigations have implicated evolutionarily conserved signaling pathways in the re-establishment of anterior-posterior (A-P), dorsal-ventral (D-V), and medial-lateral (M-L) polarity after injury. These ...
Source: Current Opinion in Genetics and Development - June 29, 2009 Category: Genetics & Stem Cells Authors: Forsthoefel DJ, Newmark PA Tags: Curr Opin Genet Dev Source Type: journals

Junctional trafficking and epithelial morphogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Epithelial monolayers are major determinants of three-dimensional tissue organization and provide the structural foundation for the body plan and all of its component organs. Epithelial cells are connected by junctional complexes containing the cell adhesion molecule E-cadherin. Adherens junctions mediate stable cohesion between cells but must be actively reorganized to allow tissue remodeling during development. Recent studies demonstrate that junctional proteins are dynamically turned over at the cell surface, even in cells that do not appear to be moving. The redistribution of E-cadherin through spatially regulated ...
Source: Current Opinion in Genetics and Development - June 23, 2009 Category: Genetics & Stem Cells Authors: Wirtz-Peitz F, Zallen JA Tags: Curr Opin Genet Dev Source Type: journals

Therapy for neuromuscular disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Research into therapeutic approaches for both recessive and dominant neuromuscular disorders has made great progress over the past few years. In the field of gene therapy, antisense-mediated exon skipping is being applied to bypass deleterious mutations in the dystrophin gene and restore dystrophin expression in animal models of muscular dystrophy. Approaches for the dominant genetic muscle diseases have turned toward elimination of the mutant gene product with anti-sense oligonucleotide therapy and RNA interference techniques. Refinements of adeno-associated viral vectors and strategies for their delivery are also lea...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Arnett AL, Chamberlain JR, Chamberlain JS Tags: Curr Opin Genet Dev Source Type: journals

Progress toward effective treatments for human photoreceptor degenerations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mutations in several dozen genes have been shown to cause inherited photoreceptor degeneration in humans and it is likely that mutations in several dozen more will eventually be identified. Careful study of these genes has provided insight into the cellular and molecular mechanisms of human photoreceptor disease and has accelerated the development of a number of different classes of therapy including: nutritional supplementation, toxin avoidance, small-molecule drugs, large-molecule drugs, gene replacement, cell replacement, and even retinal prostheses. The retina is a very favorable system for the development of novel...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Stone EM Tags: Curr Opin Genet Dev Source Type: journals

The genetics of Parkinson's syndromes: a critical review.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genetic analysis has identified many loci designated as PARK loci (OMIM #168600). Many of these loci do not refer to idiopathic Parkinson's disease which is characterized by Lewy body pathology, but rather to clinical parkinsonisms. In this review, besides reviewing the genetic of the disorder, we argue that this designation is misleading and that if we seek to understand the pathogenesis, we should study the genetics of Lewy body diseases: these include not only idiopathic Parkinson's disease, but also such disparate syndromes as Hallevorden-Spatz disease and Niemann-Pick Type C. PMID: 19419854 [PubMed - in proces...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Hardy J, Lewis P, Revesz T, Lees A, Paisan-Ruiz C Tags: Curr Opin Genet Dev Source Type: journals

Sleep and circadian rhythm disturbances: multiple genes and multiple phenotypes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sleep is regulated by two broad mechanisms: the circadian system, which generates 24-h rhythms of sleep propensity and a wake-dependent homeostatic sleep process whereby sleep pressure increases during wake and dissipates during sleep. These, in turn, regulate multiple brain structures and neurotransmitter systems. In view of the complexity of sleep it is not surprising that there is considerable variation between individuals in both sleep timing and propensity. Furthermore, marked abnormalities in sleep are commonly encountered in psychiatric and neurodegenerative disorders. Teasing apart the genetic versus environmen...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Wulff K, Porcheret K, Cussans E, Foster RG Tags: Curr Opin Genet Dev Source Type: journals

AngiomiRs--key regulators of angiogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The formation of new blood vessels through the process of angiogenesis is critical in vascular development and homeostasis. Aberrant angiogenesis leads to a variety of diseases, such as ischemia and cancer. Recent studies have revealed important roles for miRNAs in regulating endothelial cell (EC) function, especially angiogenesis. Mice with EC-specific deletion of Dicer, a key enzyme for generating miRNAs, display defective postnatal angiogenesis. Specific miRNAs (angiomiRs) have recently been shown to regulate angiogenesis in vivo. miRNA-126, an EC-restricted miRNA, regulates vascular integrity and developmental angi...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Wang S, Olson EN Tags: Curr Opin Genet Dev Source Type: journals

The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Ras/mitogen activated protein kinase (MAPK) pathway is essential in the regulation of the cell cycle, differentiation, growth and cell senescence, all of which are critical to normal development. It is therefore not surprising that its dysregulation has profound effects on development. A class of developmental syndromes, the 'RASopathies', is caused by germline mutations in genes that encode protein components of the Ras/MAPK pathway. The vast majority of these mutations result in increased signal transduction down the Ras/MAPK pathway, but usually to a lesser extent than somatic mutations associated with oncogenes...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Tidyman WE, Rauen KA Tags: Curr Opin Genet Dev Source Type: journals

The primary cilium as a cellular signaling center: lessons from disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genetic diseases known as ciliopathies have recently entered the limelight, placing new importance on a previously mysterious organelle: the primary cilium. Mutations affecting the primary cilium in both humans and animal models can lead to a plethora of distinct phenotypes including retinal degeneration, kidney cysts, and brain malformations. New findings are quickly lending insight into the functions of this cellular extension that seems to be especially important in modulation of subcellular signaling cascades at various stages of development and adult homeostasis. PMID: 19477114 [PubMed - in process] (Source: C...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Lancaster MA, Gleeson JG Tags: Curr Opin Genet Dev Source Type: journals

Duplication hotspots, rare genomic disorders, and common disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The human genome is enriched in interspersed segmental duplications that sensitize approximately 10% of our genome to recurrent microdeletions and microduplications as a result of unequal crossing over. We review the recent discovery of recurrent rearrangements within these genomic hotspots and their association with both syndromic and nonsyndromic diseases. Studies of common complex genetic disease show that a subset of these recurrent events plays an important role in autism, schizophrenia, and epilepsy. The genomic hotspot model may provide a powerful approach for understanding the role of rare variants in common di...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Mefford HC, Eichler EE Tags: Curr Opin Genet Dev Source Type: journals

Genetic advances in autism: heterogeneity and convergence on shared pathways.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The autism spectrum disorders (ASD) are a heterogeneous set of developmental disorders characterized at their core by deficits in social interaction and communication. Current psychiatric nosology groups this broad set of disorders with strong genetic liability and multiple etiologies into the same diagnostic category. This heterogeneity has challenged genetic analyses. But shared patient resources, genomic technologies, more refined phenotypes, and novel computational approaches have begun to yield dividends in defining the genetic mechanisms at work. Over the last five years, a large number of autism susceptibility l...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Bill BR, Geschwind DH Tags: Curr Opin Genet Dev Source Type: journals

Human genetics: conceptual and practical advances in the post-genome era.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19481439 [PubMed - in process] (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Davies K, Wynshaw-Boris A Tags: Curr Opin Genet Dev Source Type: journals

Asthma genetics and genomics 2009.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Asthma Genetic Association studies have been plagued by methodologic problems that are common in all studies of complex traits: small sample size, lack of replication, and lack of control of population stratification. Despite this, the field has identified 43 replicated genes from association studies. The most frequently replicated are: TNF alpha, IL4, FCERB, Adam 33, and GSTP1. Several genes have been identified by linkage and fine mapping (ADAM33, DPP10, GPR154, and PHF11) and one gene has been identified by GWAS (ORMD3). The major issue is that these genes have been looked at one at a time rather than in some more h...
Source: Current Opinion in Genetics and Development - May 31, 2009 Category: Genetics & Stem Cells Authors: Weiss ST, Raby BA, Rogers A Tags: Curr Opin Genet Dev Source Type: journals