During angiogenesis, endothelial cells are exposed to a variety of external stimuli, such as those provided by bFGF, VEGF, ephrins, and angiopoietins.20,21 Notch alters endothelial cell responsiveness by changing the expression of VEGF receptors at the cell surface of endothelial cells. Notch signaling suppressed VEGFR-2 expression, while dramatically increasing VEGFR-3 in cultured primary endothelial cells,7 schematized in Figure 2. Consistent with this reciprocal change in expression, HUVEC survival in response to VEGF-A was reduced when Notch signaling was activated and increased in response to VEGF-C.7 Thus, Notch signaling may regulate blood endothelial cell fate decisions by decreasing VEGFR-2 and increasing VEGFR-3-based signaling. In vivo, Notch signaling has been found to regulate the expression of VEGF receptors during postnatal retinal angiogenesis.22 In the retina of Dll4 heterozygous mice, disruption of Notch signaling correlated with an increase in vascular density, an increase in VEGFR-2 expression and a reduction in VEGFR-1 endothelial expression.22