Skip to content

VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling

211Citations
Citations of this article
284Readers
Mendeley users who have this article in their library.

Abstract

Angiogenesis, the growth of new blood vessels, involves specification of endothelial cells to tip cells and stalk cells, which is controlled by Notch signalling, whereas vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 have been implicated in angiogenic sprouting. Surprisingly, we found that endothelial deletion of Vegfr3, but not VEGFR-3-blocking antibodies, postnatally led to excessive angiogenic sprouting and branching, and decreased the level of Notch signalling, indicating that VEGFR-3 possesses passive and active signalling modalities. Furthermore, macrophages expressing the VEGFR-3 and VEGFR-2 ligand VEGF-C localized to vessel branch points, and Vegfc heterozygous mice exhibited inefficient angiogenesis characterized by decreased vascular branching. FoxC2 is a known regulator of Notch ligand and target gene expression, and Foxc2 +/-;Vegfr3 +/-' compound heterozygosity recapitulated homozygous loss of Vegfr3. These results indicate that macrophage-derived VEGF-C activates VEGFR-3 in tip cells to reinforce Notch signalling, which contributes to the phenotypic conversion of endothelial cells at fusion points of vessel sprouts. © 2011 Macmillan Publishers Limited. All rights reserved.

Cite

CITATION STYLE

APA

Tammela, T., Zarkada, G., Nurmi, H., Jakobsson, L., Heinolainen, K., Tvorogov, D., … Alitalo, K. (2011). VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling. Nature Cell Biology, 13(10), 1202–1213. https://doi.org/10.1038/ncb2331

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free