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

ABSTRACT: How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin ?4 (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 ?1 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.

SUBMITTER: Stenzel D

PROVIDER: S-EPMC3207109 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Stenzel Denise D Franco Claudio A CA Estrach Soline S Mettouchi Amel A Sauvaget Dominique D Rosewell Ian I Schertel Andreas A Armer Hannah H Domogatskaya Anna A Rodin Sergey S Tryggvason Karl K Collinson Lucy L Sorokin Lydia L Gerhardt Holger H Gerhardt Holger H

EMBO reports 20111028 11

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 ...[more]

PMID: 21979816

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Endothelial Notch signalling limits angiogenesis via control of artery formation.

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