VEGF and VEGF receptors in the regulation of angiogenesis

Angiogenesis is regulated by vascular endothelial growth factor (VEGF) via its high affinity receptors VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1/ KDR). To study the role of VEGF in the developing brain, we generated mice which lack a functional VEGF gene specifically in the CNS. Angiogenesis in the brain, particularly in the telencephalon, was severly impaired in these mice, indicating that vascular sprouts in the neuroectoderm are guided by VEGF gradients. VEGF activity is primarily mediated by VEGFR-2 whose induction is essential for vasculogenesis and angiogenesis. Analysis of mouse VEGFR-2 promoter/enhancer elements was used to identify critical transcriptional regulators of embryonic angiogenesis, including Ets-1 and hypoxia-inducible factor-2 (HIF-2) which cooperate functionally in endothelial cells.