Endothelial beta1 integrins regulate sprouting and network formation during vascular development

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Beta1 integrins are important regulators of vascular differentiation and development since their endothelial‐specific deletion results in embryonic lethality. In the present study we have investigated the molecular mechanisms underlying the prominent vascular abnormalities in the absence of beta1 integrins. Because of the early embryonic lethality of knock out mice we have studied endothelial cell and vessel development in beta1 integrin deficient murine embryonic stem (ES) cells. We found that vessel development was strongly defective in the mutant embryoid bodies (EBs), as only primitive and short sprouts developed from clusters of vascular precursors in beta1 integrin (−/−) EBs whereas complex network formation of endothelial tubes was observed in wild‐type EBs. The vascular defect was due to deficient beta1 integrin expression in endothelial cells as endothelial‐specific re‐expression rescued the phenotype entirely. The mechanism responsible for defective vessel formation was reduced endothelial cell migration and elongation. Moreover, the apoptosis vs proliferation rate increased during differentiation resulting in a reduction of endothelial cells. This effect was due to an elevation of peNOS and pAKT signaling molecules, respectively. Thus, endothelial beta1 integrins are determinants of vessel formation and this is mediated via different signaling pathways.