Endothelin (ET)-1 is a 21-amino-acid peptide and is thought to be involved in cellular differentiation/proliferation via the signaling cascade regulated by the ET-A receptor (ETA). ETl-ETA deficient mice show several intracardiac abnormalities. In addition to the cardiac neural crest, endocardial cushion is also involved in the formation of the four-chambered heart. The aim of the present study is to clarify whether or not an ETl-ETA signaling pathway is involved in the formation of

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... ular endocardial cushion during chick cardiogenesis. lmmunohistochemistry showed that ETA is distributed in endocardium, cushion mesenchyme, and myocardium during the formation of endocardial cushion. To examine the role of ET1-ETA signaling in cushion tissue formation using a three-dimensional collagen gel model, we cultured atrioventricular explants in the presence of an ETAantagonist. The results, which showed that the pharmacologic suppression of ETI-ETA signaling did not inhibit cushion tissue formation, strongly suggest that ET1-ETA signaling is not essential for the initiation of endothelial-mesenchymal transformation during chick cardiogenesis.