Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis

Vascular endothelial cadherin, VE-cadherin, mediates adhesion between endot helial cells and may affect vascular morphogenesis via intracellular signal ing, but the nature of these signals remains unknown. Here, targeted inacti vation (VEC-/-) or truncation of the beta-catenin-binding cytosolic domain (VECdelta C/delta C) Of the VE-cadherin gene was found not to affect assemb ly of endothelial cells in vascular plexi, but to impair their subsequent r emodeling and maturation, causing lethality at 9.5 days of gestation. Defic iency or truncation of VE-cadherin induced endothelial apoptosis and abolis hed transmission of the endothelial survival signal by VEGF-A to Akt kinase and Bc12 via reduced complex formation with VEGF receptor-2, beta-catenin, and phosphoinositide 3 (PI3)-kinase. Thus, VE-cadherin/beta-catenin signal ing controls endothelial survival.