Nonmuscle myosin II-B regulates epicardial integrity and epicardial derived mesenchymal cell maturation

Abstract

Nonmuscle myosin II-B (NMII-B) is essential for cardiac myocyte cytokinesis. The role of NMII-B in other cardiac cells is not known. Here we show that NMII-B is required in epicardial formation and function to support myocardial proliferation and coronary vessel development. Ablation of NMII-B in epicardial cells results in disruption of epicardial integrity with a loss of E-cadherin at cell-cell junctions and a focal detachment of epicardial cells from the myocardium. NMII-B ablated or blebbistatin inhibited epicardial explants demonstrate impaired mesenchymal cell maturation during epicardial epithelial-mesenchymal transition. This is manifested by an impaired invasion of collagen gels by the epicardial derived mesenchymal cells and the reorganization of the cytoskeletal structure. Although there is a marked decrease in the expression of mesenchymal genes, there is no change in Snail/E-cadherin expression. Studies from epicardial specific NMII-B ablated mice confirm the importance of NMII-B for epicardial integrity and epicardial functions in promoting cardiac myocyte proliferation and coronary vessel formation during heart development. Our findings provide a novel mechanism linking epicardial formation and epicardial function to the activity of the cytoplasmic motor protein, NMII-B.