Epicardial-specific deletion of PDGF receptors in mice resulted in defective epithelial-to-mesenchymal transition and a lack of epicardial-derived cardiac fibroblasts and coronary vascular smooth muscle cells.
Does epicardial-specific deletion of PDGF receptors disrupt epicardial epithelial-to-mesenchymal transition and cell fate determination in mice?
Signaling through both PDGF receptors is necessary for epicardial EMT and the formation of epicardial-mesenchymal derivatives, with PDGFRα having a specific role in cardiac fibroblast development.
RATIONALE: In early heart development, platelet-derived growth factor (PDGF) receptor expression in the heart ventricles is restricted to the epicardium. Previously, we showed that PDGFRβ is required for coronary vascular smooth muscle cell (cVSMC) development, but a role for PDGFRα has not been identified. Therefore, we investigated the combined and independent roles of these receptors in epicardial development. OBJECTIVE: To understand the contribution of PDGF receptors in epicardial development and epicardial-derived cell fate determination. METHODS AND RESULTS: By generating mice with epicardial-specific deletion of the PDGF receptors, we found that epicardial epithelial-to-mesenchymal transition (EMT) was defective. Sox9, an SRY-related transcription factor, was reduced in PDGF receptor-deficient epicardial cells, and overexpression of Sox9 restored epicardial migration, actin reorganization, and EMT gene expression profiles. The failure of epicardial EMT resulted in hearts that lacked epicardial-derived cardiac fibroblasts and cVSMC. Loss of PDGFRα resulted in a specific disruption of cardiac fibroblast development, whereas cVSMC development was unperturbed. CONCLUSIONS: Signaling through both PDGF receptors is necessary for epicardial EMT and formation of epicardial-mesenchymal derivatives. PDGF receptors also have independent functions in the development of specific epicardial-derived cell fates.
Smith et al. (2011) studied Epicardial development and cell fate determination. Epicardial-specific deletion of PDGF receptors was evaluated on Epicardial epithelial-to-mesenchymal transition (EMT) and cell fate determination. Epicardial-specific deletion of PDGF receptors in mice resulted in defective epithelial-to-mesenchymal transition and a lack of epicardial-derived cardiac fibroblasts and coronary vascular smooth muscle cells.