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Heidelberg, Germany

Symmons O.,Developmental Biology Unit
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

Vertebrate genes are characterized by the presence of cis-regulatory elements located at great distances from the genes they control. Alterations of these elements have been implicated in human diseases and evolution, yet little is known about how these elements interact with their surrounding sequences. A recent survey of the mouse genome with a regulatory sensor showed that the regulatory activities of these elements are not organized in a gene-centric manner, but instead are broadly distributed along chromosomes, forming large regulatory landscapes with distinct tissue-specific activities. A large genome-wide collection of expression data from this regulatory sensor revealed some basic principles of this complex genome regulatory architecture, including a substantial interplay between enhancers and other types of activities to modulate gene expression. We discuss the implications of these findings for our understanding of non-coding transcription, and of the possible consequences of structural genomic variations in disease and evolution. Source

Wennekamp S.,Developmental Biology Unit
Nature reviews. Molecular cell biology | Year: 2013

The mechanisms underlying the appearance of asymmetry between cells in the early embryo and consequently the specification of distinct cell lineages during mammalian development remain elusive. Recent experimental advances have revealed unexpected dynamics of and new complexity in this process. These findings can be integrated in a new unified framework that regards the early mammalian embryo as a self-organizing system. Source

Gaspar I.,Developmental Biology Unit
Biochemical Society Transactions | Year: 2011

RNA localization coupled to translational repression is a general mechanism for creating structural and functional asymmetry within the cell. While there are many possible ways to target an mRNA to its destination, a large fraction of the studied transcripts undertake active transport mediated by cytoskeletal elements (microtubules and actin filaments) and associated mechanoenzymes. Among the best-studied model systems of RNA localization are the oocyte and the early embryo of Drosophila melanogaster, for which many well-characterized tools have been developed to study this cell biological phenomenon in a dynamic, developing system in its in vivo context. In the present paper, we review the current evidence and models explaining the different modes of RNA localization that depend on active transport within cells. ©The Authors Journal compilation ©2011 Biochemical Society. Source

Spitz F.,Developmental Biology Unit | Furlong E.E.M.,Genome Biology Unit
Nature Reviews Genetics | Year: 2012

Developmental progression is driven by specific spatiotemporal domains of gene expression, which give rise to stereotypically patterned embryos even in the presence of environmental and genetic variation. Views of how transcription factors regulate gene expression are changing owing to recent genome-wide studies of transcription factor binding and RNA expression. Such studies reveal patterns that, at first glance, seem to contrast with the robustness of the developmental processes they encode. Here, we review our current knowledge of transcription factor function from genomic and genetic studies and discuss how different strategies, including extensive cooperative regulation (both direct and indirect), progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development. © 2012 Macmillan Publishers Limited. All rights reserved. Source

Casano A.M.,Developmental Biology Unit | Peri F.,Developmental Biology Unit
Developmental Cell | Year: 2015

Microglia are macrophages that colonize the brain during development to establish a resident population of professional phagocytes that protect against invading pathogens and contribute to brain development and homeostasis. As such, these cells sit at the interface between immunology and neurobiology. In addition to their key roles in brain physiology, microglia offer a great opportunity to address central questions in biology relating to how migrating cells find their positions in the embryo, adopt a behavior that is appropriate for that position, and interact with their local environment. We aim, in this review, to survey key recent advances in microglial research. © 2015 Elsevier Inc. Source

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