The epicardium and epicardial-derived cells:: Multiple functions in cardiac development

The epicardium develops from an extracardiac primordium, the proepicardium, which is constituted by a cluster of mesothelial cells located on the cephalic and ventral surface of the liver-sinus venosus limit (avian embryos) or on the pericardial side of the septum transversum (mammalian embryos). The proepicardium contacts the myocardial surface and gives rise to a mesothelium, which grows and progressively lines the myocardium. The epicardium generates, through a process of epithelial-mesenchymal transition, a population of epicardial-derived cells (EPDC). EPDC contribute to the development of cardiac connective tissue, fibroblasts, and the smooth muscle of cardiac vessels. Recent data suggest that EPDC can also differentiate into endothelial cells of the primary subepicardial vascular plexus. If this is confirmed, EPDC would show the same developmental properties that characterize the stem-cell-derived bipotential vascular progenitors recently described, whose differentiation into endothelium and smooth muscle is regulated by exposure to VEGF and PDGF-BB, respectively. Aside from their function in the development of cardiac connective and vascular tissue, EPDC also play an essential modulating role in the differentiation of the compact ventricular layer of the myocardium, a role which might be regulated by the transcription factor WT1 and the production of retinoic acid.