BMPER‐mediated BMP signaling promotes cardiac development

Abstract

The bone morphogenetic protein (BMP) signaling pathway regulates multiple aspects of cardiac development and endothelial cell biology. BMP signaling is tightly regulated by numerous factors, including BMP‐binding endothelial cell precursor‐derived regulator (BMPER), which can both promote and repress BMP signaling activity. In the embryonic heart, BMPER expression is limited to the endothelial cells and the endothelial‐derived cushions, suggesting that BMPER may play a role in both coronary vascular and cardiac valve development. Indeed, the coronary arteries of BMPER‐/‐ embryos are either atretic or connected distal to the semilunar valves. In vitro, BMPER‐/‐ endothelial cells have impaired tube formation and migratory ability compared with wild‐type endothelial cells. Additionally, recombinant BMPER promotes wild‐type ventricular endothelial migration in a dose‐dependent manner. Recent findings suggest that BMPER modulates epithelial‐mesenchymal transition in the developing valves, further supporting the critical role of this regulator during normal cardiac development. Together, these results indicate that BMPER‐regulated BMP signaling is critical for coronary plexus remodeling and cardiac valve formation.