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Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo
Author(s) -
Stenzel Denise,
Franco Claudio A,
Estrach Soline,
Mettouchi Amel,
Sauvaget Dominique,
Rosewell Ian,
Schertel Andreas,
Armer Hannah,
Domogatskaya Anna,
Rodin Sergey,
Tryggvason Karl,
Collinson Lucy,
Sorokin Lydia,
Gerhardt Holger
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.194
Subject(s) - microbiology and biotechnology , filopodia , basement membrane , laminin , notch signaling pathway , integrin , sprouting angiogenesis , in vivo , biology , angiogenesis , neovascularization , endothelial stem cell , cell , chemistry , in vitro , signal transduction , extracellular matrix , cancer research , actin , biochemistry
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 .