The epicardium as a source of mesenchyme for the developing heart

The primitive epicardium of the vertebrate embryo has traditionally been re garded as a rather passive mesothelium, lining the embryonic myocardium and forming the adult visceral pericardium. However, in recent years, there is an increasing evidence that the primitive epicardium is a highly dynamic e lement with supplies cells to the developing heart through a process of epi thelial-mesenchymal transition. This process seems to be more active at the atrioventricular canal and outflow tract, i.e. the cardiac segments where the endothelium transforms into mesenchyme. In this paper we review the cur rent evidence which supports such epicardial-mesenchymal transition, namely : 1) morphological features, 2) colocalization of cytokeratin and vimentin in the epicardial and subepicardial mesenchymal cells, 3) presence of commo n antigens in the transforming epicardium and endocardial cushions (fibrill in-2/JB3, ES/130, Ets-1). Recently, we have immunolocated the transcription factor Slug in the developing avian heart. Slug is a zinc-finger protein i nvolved in the formation of the neural crest, a developmental event which i mplies an epithelial-mesenchymal transition. All cells of the primitive epi cardium are Slug(+) from their differentiation until the stage HH24. Howeve r, only a fraction of the endothelial cells from the endocardial cushions a re Slug(+). We speculate that the expression of Slug marks competence of th e epicardial cells to transform into mesenchyme, although this transformati on is only achieved where an inducing signal is produced. Regarding the dev elopmental fate of the epicardial-derived cell population, there is strong evidence of its differentiation in fibroblasts and vascular smooth muscle c ells, although a contribution to the coronary endothelium cannot be discard ed.