Integrin β1 controls VE-cadherin localization and blood vessel stability

Angiogenic blood vessel growth requires several distinct but integrated cellular activities. Endothelial cell sprouting and proliferation lead to the expansion of the vasculature and give rise to a highly branched, immature plexus, which is subsequently reorganized into a mature and stable network. Although it is known that integrin-mediated cell-matrix interactions are indispensable for embryonic angiogenesis, little is known about the function of integrins in different steps of vascular morphogenesis. Here, by investigating the integrin beta 1-subunit with inducible and endothelial-specific gene targeting in the postnatal mouse retina, we show that beta 1 integrin promotes endothelial sprouting but is a negative regulator of proliferation. In maturing vessels, integrin beta 1 is indispensable for proper localization of VE-cadherin and thereby cell-cell junction integrity. The sum of our findings establishes that integrin beta 1 has critical functions in the growing and maturing vasculature, and is required for the formation of stable, non-leaky blood vessels.