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 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.
1] Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany [2] Faculty of Medicine, University of Münster, Röntgenstrasse 20, D-48149 Münster, Germany.
Hiroyuki
H
Yamamoto
1] Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany [2] Faculty of Medicine, University of Münster, Röntgenstrasse 20, D-48149 Münster, Germany.
Manuel
M
Ehling
1] Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany [2] Faculty of Medicine, University of Münster, Röntgenstrasse 20, D-48149 Münster, Germany.
Katsuhiro
K
Kato
1] Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany [2] Faculty of Medicine, University of Münster, Röntgenstrasse 20, D-48149 Münster, Germany.
Kenichi
K
Kanai
1] Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany [2] Faculty of Medicine, University of Münster, Röntgenstrasse 20, D-48149 Münster, Germany.
Max
M
van Lessen
Department of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany.
Maike
M
Frye
Electron Microscopy Unit, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany.
Dagmar
D
Zeuschner
1] Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany [2] Faculty of Medicine, University of Münster, Röntgenstrasse 20, D-48149 Münster, Germany.
Masanori
M
Nakayama
Department of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany.
Dietmar
D
Vestweber
1] Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany [2] Faculty of Medicine, University of Münster, Röntgenstrasse 20, D-48149 Münster, Germany.
Ralf H
0000000330317677
RH
Adams
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000033:anatomy & histology; D015820:Cadherins / Q000378:metabolism*; D049109:Cell Proliferation; D004727:Endothelium / Q000254:growth & development* / Q000378:metabolism; D018390:Gene Targeting; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D019012:Integrin beta1 / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008854:Microscopy, Electron; D009024:Morphogenesis / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012171:Retinal Vessels / Q000254:growth & development* / Q000648:ultrastructure; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D019012:Integrin beta1; D034741:RNA, Small Interfering; D000099152:Cadherin 5