COMMON EPICARDIAL ORIGIN OF CORONARY VASCULAR SMOOTH-MUSCLE, PERIVASCULAR FIBROBLASTS, AND INTERMYOCARDIAL FIBROBLASTS IN THE AVIAN HEART

Previous studies have shown that during avian heart development, epica rdial and coronary vascular smooth muscle precursors are derived from the proepicardium, a derivative of the developing liver. This finding led to a model of coronary vascular development in which epicardial ce lls migrate over the postlooped heart, followed by migration of commit ted endothelial and smooth muscle precursors from the proepicardium th rough the subepicardial matrix where the coronary arteries develop. He re we show that epicardial cells undergo epithelial-mesenchymal transf ormation to become coronary vascular smooth muscle, perivascular fibro blasts, and intermyocardial fibroblasts. We began by establishing prim ary cultures of quail epicardial cells that retain morphologic and ant igenic identity to epicardial cells in vivo. Quail epicardial monolaye rs stimulated with serum or vascular growth factors produced invasive mesenchyme in collagen gels. Chick epicardial cells labeled in ovo wit h DiI invaded the subepicardial extracellular matrix, demonstrating th at mesenchymal transformation of epicardium occurs in vivo. To determi ne the fates of epicardially derived mesenchymal cells, quail epicardi al cells labeled in vitro with LacZ were grafted into the pericardial space of E2 chicks. These cells attached to the heart, formed a chimer ic epicardium, invaded the subepicardial matrix and myocardial wall, a nd became coronary vascular smooth muscle, perivascular fibroblasts, a nd intermyocardial fibroblasts, demonstrating the common epicardial or igin of these cell types. A general model of coronary vascular develop ment should now include epicardial-mesenchymal transformation and dire ct participation of mesenchyme derived from the epicardium in coronary morphogenesis. (C) 1998 Academic Press.