Development 129, 3185-3194 (2002) 3185 Printed in Great Britain © The Company of Biologists Limited 2002 DEV3650 Competency of embryonic cardiomyocytes to undergo Purkinje fiber differentiation is regulated by endothelin receptor expression Nobuyuki Kanzawa, Clifton P. Poma, Kimiko Takebayashi-Suzuki, Kevin G. Diaz, John Layliev and Takashi Mikawa* Department of Cell Biology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021, USA *Author for correspondence (e-mail:
[email protected]) Accepted 27 March 2002 SUMMARY Purkinje fibers of the cardiac conduction system embryonic chick heart. Whole-mount in situ hybridization differentiate from heart muscle cells during embryogenesis. analyses revealed that ETA was ubiquitously expressed in In the avian heart, Purkinje fiber differentiation takes both ventricular and atrial myocardium during heart place along the endocardium and coronary arteries. To development, while ETB was predominantly expressed in date, only the vascular cytokine endothelin (ET) has been the atrium and the left ventricle. ETB2 expression was demonstrated to induce embryonic cardiomyocytes to detected in valve leaflets but not in the myocardium. RNase differentiate into Purkinje fibers. This ET-induced protection assays showed that ventricular expression of Purkinje fiber differentiation is mediated by binding of ET ETA and ETB increased until Purkinje fiber differentiation to its transmembrane receptors that are expressed by began. Importantly, the levels of both receptor isotypes myocytes. Expression of ET converting enzyme 1, which decreased after this time. Retrovirus-mediated produces a biologically active ET ligand, begins in cardiac overexpression of ETA in ventricular myocytes in which endothelia, both arterial and endocardial, at initiation of endogenous ET receptors had been downregulated, conduction cell differentiation and continues throughout enhanced their responsiveness to ET, allowing them to heart development.