During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types which contribute to the coronary vessels. The type III transforming growth factor-β receptor (TGFβR3) is required for epicardial cell invasion and development of coronary vasculature in vivo. Bone Morphogenic Protein-2 (BMP2) is a driver of epicardial cell migration. Utilizing a primary epicardial cell line derived from Tgfbr3+/+ and Tgfbr3−/− mouse embryos, we show that Tgfbr3−/− epicardial cells are deficient in BMP2 mRNA expression. Tgfbr3−/− epicardial cells are deficient in 2-dimensional migration relative to Tgfbr3+/+ cells; BMP2 induces cellular migration to Tgfbr3+/+ levels without affecting proliferation. We further demonstrate that Src kinase activity is required for BMP2 driven Tgfbr3−/− migration. BMP2 also requires Src for filamentous actin polymerization in Tgfbr3−/− epicardial cells. Taken together, our data identifies a novel pathway in epicardial cell migration required for development of the coronary vessels.
|Date made available||2016|