Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo
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Denise Stenzel Claudio A Franco Soline Estrach Amel Mettouchi Dominique Sauvaget Ian Rosewell Andreas Schertel Hannah Armer Anna Domogatskaya Sergey Rodin Karl Tryggvason Lucy Collinson Lydia Sorokin Holger GerhardtAbstract
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.
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Publisher website (DOI) 10.1038/embor.2011.194
Europe PubMed Central 21979816
Pubmed 21979816
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