Red Light, Green Light: Signals That Control Endothelial Cell Proliferation during Embryonic Vascular Development

Abstract

The proper regulation of endothelial cell proliferation is critical for vasculardevelopment in the embryo. VEGF-A and bFGF, which are important in the induction ofmesodermal progenitors to form a capillary plexus, are also key mitogenic signals.Disruption in VEGF-A or bFGF decreases endothelial cell proliferation and haltsvascular development. While stimulation of endothelial cell proliferation is necessaryduring vasculogenesis, inhibitory signals such as TGF-?1 and retinoic acid are equallyimportant and required to inhibit endothelial cell proliferation. These signals andactivation of numerous downstream pathways must be properly integrated withextracellular matrix proteins and integrin receptor signaling in order to form theembryonic vasculature. This coordination of mitogenic and anti-proliferative signalsneeded to form a circulatory network in the embryo may be unique relative toneovascularization in adult tissues where mitogenic stimulation promotes proliferation ofpreviously quiescent endothelial cells to repair and expand existing vasculatures.