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Retinoic Acid Regulates Differentiation of the Secondary Heart Field and TGFβ-Mediated Outflow Tract Septation

Retinoic Acid Regulates Differentiation of the Secondary Heart Field and TGFβ-Mediated Outflow Tract Septation

Authors :
Li, Peng
Pashmforoush, Mohammad
Sucov, Henry M.
Source :
Developmental Cell. Mar2010, Vol. 18 Issue 3, p480-485. 6p.
Publication Year :
2010

Abstract

Summary: In many experimental models and clinical examples, defects in the differentiation of the second heart field (SHF) and heart outflow tract septation defects are combined, although the mechanistic basis for this relationship has been unclear. We found that as the initial SHF population incorporates into the outflow tract, it is replenished from the surrounding progenitor territory. In retinoic acid (RA) receptor mutant mice, this latter process fails, and the outflow tract is shortened and misaligned as a result. As an additional consequence, the outflow tract is misspecified along its proximal-distal axis, which results in ectopic expression of TGFβ2 and ectopic mesenchymal transformation of the endocardium. Reduction of TGFβ2 gene dosage in the RA receptor-deficient background restores septation but does not rescue alignment defects, indicating that excess TGFβ causes septation defects. This may be a common pathogenic pathway when second heart field and septation defects are coupled. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
15345807
Volume :
18
Issue :
3
Database :
Academic Search Index
Journal :
Developmental Cell
Publication Type :
Academic Journal
Accession number :
48604749
Full Text :
https://doi.org/10.1016/j.devcel.2009.12.019