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

First Author  Stenzel D Year  2011
Journal  EMBO Rep Volume  12
Issue  11 Pages  1135-43
PubMed ID  21979816 Mgi Jnum  J:178535
Mgi Id  MGI:5299253 Doi  10.1038/embor.2011.194
Citation  Stenzel D, et al. (2011) Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo. EMBO Rep 12(11):1135-43
abstractText  How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin alpha4 (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 beta1 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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