Document Detail

Tbx5-hedgehog molecular networks are essential in the second heart field for atrial septation.
MedLine Citation:
PMID:  22898775     Owner:  NLM     Status:  MEDLINE    
The developmental mechanisms underlying human congenital heart disease (CHD) are poorly understood. Atrial septal defects (ASDs) can result from haploinsufficiency of cardiogenic transcription factors including TBX5. We demonstrated that Tbx5 is required in the second heart field (SHF) for atrial septation in mice. Conditional Tbx5 haploinsufficiency in the SHF but not the myocardium or endocardium caused ASDs. Tbx5 SHF knockout embryos lacked atrial septum progenitors. We found that Tbx5 mutant SHF progenitors demonstrated cell-cycle progression defects and that Tbx5 regulated cell-cycle progression genes including Cdk6. Activated hedgehog (Hh) signaling rescued ASDs in Tbx5 mutant embryos, placing Tbx5 upstream or parallel to Hh in cardiac progenitors. Tbx5 regulated SHF Gas1 and Osr1 expression, supporting both pathways. These results describe a SHF Tbx5-Hh network required for atrial septation. A paradigm defining molecular requirements in SHF cardiac progenitors for cardiac septum morphogenesis has implications for the ontogeny of CHD.
Linglin Xie; Andrew D Hoffmann; Ozanna Burnicka-Turek; Joshua M Friedland-Little; Ke Zhang; Ivan P Moskowitz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Developmental cell     Volume:  23     ISSN:  1878-1551     ISO Abbreviation:  Dev. Cell     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-17     Completed Date:  2012-11-01     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  280-91     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Arteries / metabolism
Cell Line
Cell Proliferation
Embryo, Mammalian / metabolism
Gene Expression Regulation, Developmental
Heart Septum / embryology,  metabolism*
Hedgehog Proteins / deficiency,  metabolism
Neovascularization, Physiologic
Signal Transduction*
Stem Cells / cytology,  metabolism
T-Box Domain Proteins / genetics,  metabolism*
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Hedgehog Proteins; 0/Shh protein, mouse; 0/T-Box Domain Proteins; 0/T-box transcription factor 5

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