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

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 Gerhardt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

104 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1135-1143
Number of pages9
JournalEMBO Reports
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 2011
Externally publishedYes

Keywords

  • integrin
  • laminin
  • Notch signalling
  • sprouting angiogenesis
  • vascular basement membrane

Fingerprint

Dive into the research topics of 'Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo'. Together they form a unique fingerprint.

Cite this