Document Detail

Regulation of heart valve morphogenesis by Eph receptor ligand, ephrin-A1.
MedLine Citation:
PMID:  20960543     Owner:  NLM     Status:  MEDLINE    
Disease or malformation of heart valves is one of the leading causes of morbidity and mortality in both children and adults. These congenital anomalies can remain undetected until cardiac function is compromised, making it important to understand the underlying nature of these disorders. Here we show that ephrin-A1, a ligand for class A Eph receptor tyrosine kinases, regulates cardiac valve formation. Exogenous ephrin-A1-Fc or overexpression of ephrin-A1 in the heart inhibits epithelial-to-mesenchymal transformation (EMT) in chick atrioventricular cushion explants. In contrast, overexpression of wild-type EphA3 receptor promotes EMT via a kinase-dependent mechanism. To analyze ephrin-A1 in vivo, we generated an ephrin-A1 knockout mouse through gene targeting. Ephrin-A1 null animals are viable but exhibit impaired cardiac function. Loss of ephrin-A1 results in thickened aortic and mitral valves in newborn and adult animals. Analysis of early embryonic hearts revealed increased cellularity in outflow tract endocardial cushions and elevated mesenchymal marker expression, suggesting that excessive numbers of cells undergo EMT. Taken together, these data indicate that ephrin-A1 regulates cardiac valve development, making ephrin-A1-deficient mice a novel model for congenital heart defects.
Leslie A Frieden; Todd A Townsend; David B Vaught; Daniel M Delaughter; Yoonha Hwang; Joey V Barnett; Jin Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-10-19
Journal Detail:
Title:  Developmental dynamics : an official publication of the American Association of Anatomists     Volume:  239     ISSN:  1097-0177     ISO Abbreviation:  Dev. Dyn.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-03-15     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  9201927     Medline TA:  Dev Dyn     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3226-34     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley-Liss, Inc.
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MeSH Terms
Ephrin-A1 / genetics,  metabolism*
Heart / embryology*
Heart Valves / embryology*
Mice, Knockout
Morphogenesis / genetics,  physiology*
Grant Support
CA114301/CA/NCI NIH HHS; CA95004/CA/NCI NIH HHS; HL0952551/HL/NHLBI NIH HHS; R01 CA095004/CA/NCI NIH HHS; R01 CA095004-09/CA/NCI NIH HHS; R01 CA114301/CA/NCI NIH HHS; R01 CA114301-05/CA/NCI NIH HHS; R01 HL085708/HL/NHLBI NIH HHS; R01 HL085708-03/HL/NHLBI NIH HHS; T32 GM007628/GM/NIGMS NIH HHS; T32 GM007628/GM/NIGMS NIH HHS; T32 GM007628-28/GM/NIGMS NIH HHS; T32 HD07390/HD/NICHD NIH HHS; T32 HL007751/HL/NHLBI NIH HHS; T32 HL007751-14/HL/NHLBI NIH HHS
Reg. No./Substance:

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

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