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Dev Dyn. 2008 Apr;237(4):1144-52. doi: 10.1002/dvdy.21502.

Notch2 is required for the proliferation of cardiac neural crest-derived smooth muscle cells.

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1
Division of Cellular and Gene Therapies, Food and Drug Administration Bethesda, Maryland 20892, USA.

Abstract

Mutations in Notch receptors and their ligands have been identified as the cause of human congenital heart diseases, indicating the importance of the Notch signaling pathway during heart development. In our study, we use Cre-Lox technology to inactivate Notch2 in several cardiac cell lineages to determine the functional requirements for Notch2 during mammalian heart development. Inactivation of Notch2 in cardiac neural crest cells resulted in abnormally narrow aortas and pulmonary arteries due to a decrease in smooth muscle tissue. The reduction in smooth muscle tissue was not due to cell migration defects but instead was found to be caused by less proliferation in smooth muscle cells during mid to late gestation. Our findings demonstrate that Notch2 is required cell autonomously for proper formation of the heart outflow tract and provides insights into the role of Notch2 in vascular smooth muscle development and the cardiovascular defects associated with Alagille syndrome.

PMID:
18330927
DOI:
10.1002/dvdy.21502
[Indexed for MEDLINE]
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