Graphic overview of heart development and endothelial-mesenchymal transformation (EMT). As the heart tube develops it contains three layers, an inner lining of endothelial cells, a middle separating layer of ECM referred to as cardiac jelly, and an outer layer of myocardium. As valves form, a subset of the endothelial cells undergo EMT by delaminating, differentiating, and then migrating into the cardiac jelly. Then, in a process that is poorly understood, local swellings of cardiac jelly and mesenchymal cells (cardiac cushions) undergo remodeling and form heart valves. Reprinted from Armstrong, E. J., & Bischoff, J. (2004). Heart valve development: endothelial cell signaling and differentiation. Circ Res, 95(5), 459–470 with permission from Wolters Kluwer Heath.