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Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo

Item Type:Article
Title:Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo
Creators Name:Stenzel, D. and Franco, C.A. and Estrach, S. and Mettouchi, A. and Sauvaget, D. and Rosewell, I. and Schertel, A. and Armer, H. and Domogatskaya, A. and Rodin, S. and Tryggvason, K. and Collinson, L. and Sorokin, L. and Gerhardt, H.
Abstract:How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin α4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin β1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo.
Keywords:Integrin, Laminin, Notch Signalling, Sprouting Angiogenesis, Vascular Basement Membrane, Animals, Mice
Source:EMBO Reports
ISSN:1469-221X
Publisher:Nature Publishing Group (U.K.)
Volume:12
Number:11
Page Range:1135-1143
Date:1 November 2011
Official Publication:https://doi.org/10.1038/embor.2011.194
PubMed:View item in PubMed

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