{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:10:15Z","timestamp":1789002615765,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2010,10,19]],"date-time":"2010-10-19T00:00:00Z","timestamp":1287446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010A1, a ligand for class A Eph receptor tyrosine kinases, regulates cardiac valve formation. Exogenous ephrin\u2010A1\u2010Fc or overexpression of ephrin\u2010A1 in the heart inhibits epithelial\u2010to\u2010mesenchymal transformation (EMT) in chick atrioventricular cushion explants. In contrast, overexpression of wild\u2010type EphA3 receptor promotes EMT via a kinase\u2010dependent mechanism. To analyze ephrin\u2010A1 in vivo, we generated an ephrin\u2010A1 knockout mouse through gene targeting. Ephrin\u2010A1 null animals are viable but exhibit impaired cardiac function. Loss of ephrin\u2010A1 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\u2010A1 regulates cardiac valve development, making ephrin\u2010A1\u2010deficient mice a novel model for congenital heart defects. Developmental Dynamics 239:3226\u20133234, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.22458","type":"journal-article","created":{"date-parts":[[2010,10,19]],"date-time":"2010-10-19T12:12:45Z","timestamp":1287490365000},"page":"3226-3234","source":"Crossref","is-referenced-by-count":44,"title":["Regulation of heart valve morphogenesis by Eph receptor ligand, ephrin\u2010A1"],"prefix":"10.1002","volume":"239","author":[{"given":"Leslie A.","family":"Frieden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Townsend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Vaught","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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