Document Detail

Tbx5 is dispensable for forelimb outgrowth.
MedLine Citation:
PMID:  17138667     Owner:  NLM     Status:  MEDLINE    
Tbx5 is essential for initiation of the forelimb, and its deletion in mice results in the failure of forelimb formation. Misexpression of dominant-negative forms of Tbx5 results in limb truncations, suggesting Tbx5 is also required for forelimb outgrowth. Here we show that Tbx5 is expressed throughout the limb mesenchyme in progenitors of cartilage, tendon and muscle. Using a tamoxifeninducible Cre transgenic line, we map the time frame during which Tbx5 is required for limb development. We show that deletion of Tbx5 subsequent to limb initiation does not impair limb outgrowth. Furthermore, we distinguish two distinct phases of limb development: a Tbx5-dependent limb initiation phase, followed by a Tbx5-independent limb outgrowth phase. In humans, mutations in the T-box transcription factor TBX5 are associated with the dominant disorder Holt-Oram syndrome (HOS), which is characterised by malformations in the forelimb and heart. Our results demonstrate a short temporal requirement for Tbx5 during early limb development, and suggest that the defects found in HOS arise as a result of disrupted TBX5 function during this narrow time window.
Peleg Hasson; Joanne Del Buono; Malcolm P O Logan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-30
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  134     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-13     Completed Date:  2007-03-28     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  85-92     Citation Subset:  IM    
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MeSH Terms
Animals, Newborn
Embryo, Mammalian
Embryonic Induction / drug effects
Fluorescent Antibody Technique, Indirect
Forelimb / embryology*
Gene Expression Regulation, Developmental
In Situ Hybridization
Mesoderm / metabolism
Mice, Transgenic
Models, Biological
T-Box Domain Proteins / genetics,  metabolism*
Tamoxifen / pharmacology
Time Factors
Grant Support
MC_U117560477//Medical Research Council
Reg. No./Substance:
0/T-Box Domain Proteins; 0/T-box transcription factor 5; 094ZI81Y45/Tamoxifen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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