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Distinct roles of Hand2 in initiating polarity and posterior Shh expression during the onset of mouse limb bud development

PLoS genetics, 2010-04, Vol.6 (4), p.e1000901-e1000901 [Peer Reviewed Journal]

COPYRIGHT 2010 Public Library of Science ;COPYRIGHT 2010 Public Library of Science ;This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. 2010 ;2010 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Galli A, Robay D, Osterwalder M, Bao X, Bénazet J-D, et al. (2010) Distinct Roles of Hand2 in Initiating Polarity and Posterior Shh Expression during the Onset of Mouse Limb Bud Development. PLoS Genet 6(4): e1000901. doi:10.1371/journal.pgen.1000901 ;ISSN: 1553-7404 ;ISSN: 1553-7390 ;EISSN: 1553-7404 ;DOI: 10.1371/journal.pgen.1000901 ;PMID: 20386744

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Title:
Distinct roles of Hand2 in initiating polarity and posterior Shh expression during the onset of mouse limb bud development
Author: Galli, Antonella ; Robay, Dimitri ; Osterwalder, Marco ; Bao, Xiaozhong ; Bénazet, Jean-Denis ; Tariq, Muhammad ; Paro, Renato ; Mackem, Susan ; Zeller, Rolf
Tabin, Clifford J.
Subjects: Animals ; Apoptosis ; Asymmetry ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Body Patterning - genetics ; Cellular signal transduction ; Chromatin - metabolism ; Developmental Biology ; Developmental Biology/Embryology ; Developmental Biology/Molecular Development ; Developmental Biology/Morphogenesis and Cell Biology ; Developmental Biology/Organogenesis ; Developmental Biology/Pattern Formation ; Embryo, Mammalian - metabolism ; Experiments ; Extremities (Anatomy) ; Fingers & toes ; Gene expression ; Gene Expression Regulation, Developmental ; Genetic aspects ; Genetic regulation ; Genetics and Genomics ; Genetics and Genomics/Gene Function ; Hedgehog Proteins - genetics ; Hedgehog Proteins - metabolism ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Limb Buds - embryology ; Medical research ; Mice ; Mice, Transgenic ; Mutation ; Physiological aspects ; Proteins ; Studies ; Transcription Factors - genetics ; Transcription Factors - metabolism
Is Part Of: PLoS genetics, 2010-04, Vol.6 (4), p.e1000901-e1000901
Description: The polarization of nascent embryonic fields and the endowment of cells with organizer properties are key to initiation of vertebrate organogenesis. One such event is antero-posterior (AP) polarization of early limb buds and activation of morphogenetic Sonic Hedgehog (SHH) signaling in the posterior mesenchyme, which in turn promotes outgrowth and specifies the pentadactylous autopod. Inactivation of the Hand2 transcriptional regulator from the onset of mouse forelimb bud development disrupts establishment of posterior identity and Shh expression, which results in a skeletal phenotype identical to Shh deficient limb buds. In wild-type limb buds, Hand2 is part of the protein complexes containing Hoxd13, another essential regulator of Shh activation in limb buds. Chromatin immunoprecipitation shows that Hand2-containing chromatin complexes are bound to the far upstream cis-regulatory region (ZRS), which is specifically required for Shh expression in the limb bud. Cell-biochemical studies indicate that Hand2 and Hoxd13 can efficiently transactivate gene expression via the ZRS, while the Gli3 repressor isoform interferes with this positive transcriptional regulation. Indeed, analysis of mouse forelimb buds lacking both Hand2 and Gli3 reveals the complete absence of antero-posterior (AP) polarity along the entire proximo-distal axis and extreme digit polydactyly without AP identities. Our study uncovers essential components of the transcriptional machinery and key interactions that set-up limb bud asymmetry upstream of establishing the SHH signaling limb bud organizer.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1553-7404
ISSN: 1553-7390
EISSN: 1553-7404
DOI: 10.1371/journal.pgen.1000901
PMID: 20386744
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
Public Library of Science (PLoS)
ProQuest Central
DOAJ Directory of Open Access Journals

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Distinct roles of Hand2 in initiating polarity and posterior Shh expression during the onset of mouse limb bud development

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