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VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Gerhardt, H, Golding, M, Fruttiger, M, Ruhrberg, C, Lundkvist, A, Abramsson, A, Jeltsch, M, Mitchell, Christopher, Alitalo, K, Shima, D and Betsholtz, C (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. JOURNAL OF CELL BIOLOGY, 161 (6). pp. 1163-1177. [Journal article]

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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.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Molecular Medicine
Biomedical Sciences Research Institute > Molecular Medicine > Vascular Medicine
ID Code:9471
Deposited By:Dr Christopher Mitchell
Deposited On:23 Jan 2010 16:04
Last Modified:10 Jun 2010 10:59

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