title: 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 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.
authors: Vascular Biology Laboratory, London Research Institute - Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors: Denise
authors: D
authors: Stenzel
authors: Claudio A
authors: CA
authors: Franco
authors: Soline
authors: S
authors: Estrach
authors: Amel
authors: A
authors: Mettouchi
authors: Dominique
authors: D
authors: Sauvaget
authors: Ian
authors: I
authors: Rosewell
authors: Andreas
authors: A
authors: Schertel
authors: Hannah
authors: H
authors: Armer
authors: Anna
authors: A
authors: Domogatskaya
authors: Sergey
authors: S
authors: Rodin
authors: Karl
authors: K
authors: Tryggvason
authors: Lucy
authors: L
authors: Collinson
authors: Lydia
authors: L
authors: Sorokin
authors: Holger
authors: H
authors: Gerhardt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002135:Calcium-Binding Proteins; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D016023:Integrins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007797:Laminin / Q000172:deficiency / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; C501370:Lama4 protein, mouse; D007797:Laminin; D008565:Membrane Proteins; D051880:Receptors, Notch