VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia

H Gerhardt, M Golding, M Fruttiger, C Ruhrberg, A Lundkvist, A Abramsson, M Jeltsch, Christopher Mitchell, K Alitalo, D Shima, C Betsholtz

Research output: Contribution to journalArticle

1650 Citations (Scopus)

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.
LanguageEnglish
Pages1163-1177
JournalJournal of Cell Biology
Volume161
Issue number6
Publication statusPublished - Jun 2003

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Pseudopodia
Vascular Endothelial Growth Factor A
Endothelial Cells
Blood Vessels
Vascular Endothelial Growth Factor Receptor
Cell Movement
Retina
Population

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Gerhardt, H., Golding, M., Fruttiger, M., Ruhrberg, C., Lundkvist, A., Abramsson, A., ... Betsholtz, C. (2003). VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. Journal of Cell Biology, 161(6), 1163-1177.
Gerhardt, H ; Golding, M ; Fruttiger, M ; Ruhrberg, C ; Lundkvist, A ; Abramsson, A ; Jeltsch, M ; Mitchell, Christopher ; Alitalo, K ; Shima, D ; Betsholtz, C. / VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. In: Journal of Cell Biology. 2003 ; Vol. 161, No. 6. pp. 1163-1177.
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Gerhardt, H, Golding, M, Fruttiger, M, Ruhrberg, C, Lundkvist, A, Abramsson, A, Jeltsch, M, Mitchell, C, Alitalo, K, Shima, D & Betsholtz, C 2003, 'VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia', Journal of Cell Biology, vol. 161, no. 6, pp. 1163-1177.

VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. / Gerhardt, H; Golding, M; Fruttiger, M; Ruhrberg, C; Lundkvist, A; Abramsson, A; Jeltsch, M; Mitchell, Christopher; Alitalo, K; Shima, D; Betsholtz, C.

In: Journal of Cell Biology, Vol. 161, No. 6, 06.2003, p. 1163-1177.

Research output: Contribution to journalArticle

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AB - 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.

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Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. Journal of Cell Biology. 2003 Jun;161(6):1163-1177.