VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia

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Item Type:	Article
Title:	VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia
Creators Name:	Gerhardt, H., Golding, M., Fruttiger, M., Ruhrberg, C., Lundkvist, A., Abramsson, A., Jeltsch, M., Mitchell, C., Alitalo, K., Shima, D. and Betsholtz, C.
Abstract:	Vascular endothelial growth factor (VEGF-A) is a major regulator of blood vessel formation and function. It controls several processes in endothelial cells, such as proliferation, survival, and migration, but it is not known how these are coordinately regulated to result in more complex morphogenetic events, such as tubular sprouting, fusion, and network formation. We show here that VEGF-A controls angiogenic sprouting in the early postnatal retina by guiding filopodial extension from specialized endothelial cells situated at the tips of the vascular sprouts. The tip cells respond to VEGF-A only by guided migration; the proliferative response to VEGF-A occurs in the sprout stalks. These two cellular responses are both mediated by agonistic activity of VEGF-A on VEGF receptor 2. Whereas tip cell migration depends on a gradient of VEGF-A, proliferation is regulated by its concentration. Thus, vessel patterning during retinal angiogenesis depends on the balance between two different qualities of the extracellular VEGF-A distribution, which regulate distinct cellular responses in defined populations of endothelial cells.
Keywords:	VEGF, Endothelial Cell, Filopodia, Astrocyte, Migration, Proliferation, Animals, Mice
Source:	Journal of Cell Biology
ISSN:	0021-9525
Publisher:	Rockefeller University Press
Volume:	161
Number:	6
Page Range:	1163-1177
Date:	23 June 2003
Official Publication:	https://doi.org/10.1083/jcb.200302047
PubMed:	View item in PubMed

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