Red light, green light: signals that control endothelial cell proliferation during embryonic vascular development.

The proper regulation of endothelial cell proliferation is critical for vascular development in the embryo. VEGF-A and bFGF, which are important in the induction of mesodermal progenitors to form a capillary plexus, are also key mitogenic signals. Disruption in VEGF-A or bFGF decreases endothelial cell proliferation and halts vascular development. While stimulation of endothelial cell proliferation is necessary during vasculogenesis, inhibitory signals such as TGF-beta1 and retinoic acid are equally important and required to inhibit endothelial cell proliferation. These signals and activation of numerous downstream pathways must be properly integrated with extracellular matrix proteins and integrin receptor signaling in order to form the embryonic vasculature. This coordination of mitogenic and anti-proliferative signals needed to form a circulatory network in the embryo may be unique relative to neovascularization in adult tissues where mitogenic stimulation promotes proliferation of previously quiescent endothelial cells to repair and expand existing vasculature.