Integrin β1 controls VE-cadherin localization and blood vessel stability

Hiroyuki Yamamoto, Manuel Ehling, Katsuhiro Kato, Kenichi Kanai, Max van Lessen, Maike Frye, Dagmar Zeuschner, Masanori Nakayama, Dietmar Vestweber and Ralf H. Adams ()
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Hiroyuki Yamamoto: Max Planck Institute for Molecular Biomedicine
Manuel Ehling: Max Planck Institute for Molecular Biomedicine
Katsuhiro Kato: Max Planck Institute for Molecular Biomedicine
Kenichi Kanai: Max Planck Institute for Molecular Biomedicine
Max van Lessen: Max Planck Institute for Molecular Biomedicine
Maike Frye: Max Planck Institute for Molecular Biomedicine
Dagmar Zeuschner: Electron Microscopy Unit, Max Planck Institute for Molecular Biomedicine
Masanori Nakayama: Max Planck Institute for Molecular Biomedicine
Dietmar Vestweber: Max Planck Institute for Molecular Biomedicine
Ralf H. Adams: Max Planck Institute for Molecular Biomedicine

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract 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 β1-subunit with inducible and endothelial-specific gene targeting in the postnatal mouse retina, we show that β1 integrin promotes endothelial sprouting but is a negative regulator of proliferation. In maturing vessels, integrin β1 is indispensable for proper localization of VE-cadherin and thereby cell–cell junction integrity. The sum of our findings establishes that integrin β1 has critical functions in the growing and maturing vasculature, and is required for the formation of stable, non-leaky blood vessels.

Date: 2015
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DOI: 10.1038/ncomms7429

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