PDGF-A as an epicardial mitogen during heart development.

In the developing heart, reciprocal interactions between the epicardium and myocardium drive further sublineage specification and ventricular chamber morphogenesis. Several observations suggest that the epicardium is a source of secreted factors that influence cardiomyocyte proliferation, and these factors may have other roles as well. However, the identity of these epicardial factors remains mostly unknown. We have identified platelet-derived growth factor-A (PDGF-A) as one of several mitogens expressed by the rat EMC epicardial cell line (epicardial mesothelial cells), by embryonic epicardium and myocardium during mouse heart development, and by adult epicardium. Expression of the cognate receptor gene Pdgfra was detected in the epicardium, although a low level of expression in myocardium could not be ruled out. To address the potential role of PDGF signaling in heart development, we mutated both PDGF receptor genes in the myocardial and mesodermal compartments of the heart; however, this did not result in an observable cardiac phenotype. This finding suggests that mesodermal PDGF signaling is not essential in heart development, although its role may be redundant with other signaling pathways. Indeed, our results demonstrate the presence of additional mitogens that may have such an overlapping role.