Platelet-Derived Growth Factor Receptor β Signaling Is Required for Efficient Epicardial Cell Migration and Development of Two Distinct Coronary Vascular Smooth Muscle Cell Populations

Abstract

The epicardium plays an essential role in coronary artery formation and myocardial development, but signals controlling the development and differentiation of this tissue are not well understood. To investigate the role of platelet-derived growth factor receptor (PDGFR)β in development of epicardial-derived vascular smooth muscle cells (VSMCs), we examined PDGFRβ−/− and PDGFRβ epicardial mutant hearts. We found that PDGFRβ−/− hearts failed to form dominant coronary vessels on the ventral heart surface, had a thinned myocardium, and completely lacked coronary VSMCs (cVSMCs). This constellation of defects was consistent with a primary defect in the epicardium. To verify that these defects were specific to epicardial derivatives, we generated mice with an epicardial deletion of PDGFRβ that resulted in reduced cVSMCs distal to the aorta. The regional absence of cVSMCs suggested that cVSMCs could arise from 2 sources, epicardial and nonepicardial, and that both were dependent on PDGFRβ. In the absence of PDGFR...