Document Detail

Notch signaling in cardiac valve development and disease.
MedLine Citation:
PMID:  21563298     Owner:  NLM     Status:  Publisher    
The Notch pathway is an intercellular signaling mechanism involved in multiple cell-to-cell communication processes that regulate cell fate specification, differentiation, and tissue patterning during embryogenesis and adulthood. Functional studies in the mouse have shown that a Hey-Bmp2 regulatory circuit restricts Bmp2 expression to presumptive valve myocardium (atrioventricular canal and outflow tract). Likewise, a Notch-Hey-Bmp2 axis represses Bmp2 in the endocardium. During cardiac valve formation, endocardial Notch signaling activates the epithelial-mesenchyme transition (EMT) that will give rise to the cardiac valve primordia. During this process, Notch integrates with myocardially derived signals (Bmp2 or Bmp4) to promote, via Snail1/2 activation a complete, invasive EMT in presumptive valve tissue. In humans, mutations in Notch signaling components are associated with several congenital disorders involving malformed valves, aortic arch, and defective chamber septation. Data suggest that the same embryonic Notch-Hey-Bmp2 regulatory axis is active in the adult valve. This review examines the experimental evidence supporting a role for Notch in heart valve development and homeostasis, and how altered Notch signaling may lead to valve disease in the newborn and adult. Birth Defects Research (Part A) 2011. © 2011 Wiley-Liss, Inc.
Donal Macgrogan; Luis Luna-Zurita; José Luis de la Pompa
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-11
Journal Detail:
Title:  Birth defects research. Part A, Clinical and molecular teratology     Volume:  -     ISSN:  1542-0760     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101155107     Medline TA:  Birth Defects Res A Clin Mol Teratol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Laboratorio de Señalizacion Intercelular, Dpto. de Biología del Desarrollo Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
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