TY - JOUR TI - VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia EP - 1177 AV - public Y1 - 2003/06/23/ ID - discovery16410 N2 - 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. PB - ROCKEFELLER UNIV PRESS KW - VEGF KW - endothelial cell KW - filopodia KW - astrocyte KW - migration KW - proliferation KW - VASCULAR-PERMEABILITY FACTOR KW - GROWTH-FACTOR KW - RETINAL VASCULATURE KW - BRANCHING MORPHOGENESIS KW - CEREBRAL-CORTEX KW - BLOOD-VESSELS KW - TUMOR-CELLS KW - RAT AORTA KW - EXPRESSION KW - RECEPTOR SP - 1163 VL - 161 IS - 6 SN - 0021-9525 UR - https://discovery.ucl.ac.uk/id/eprint/16410/ JF - J CELL BIOL A1 - Gerhardt, H A1 - Golding, M A1 - Fruttiger, M A1 - Ruhrberg, C A1 - Lundkvist, A A1 - Abramsson, A A1 - Jeltsch, M A1 - Mitchell, C A1 - Alitalo, K A1 - Shima, D A1 - Betsholtz, C ER -