01766nas a2200133   4500008004100000022001400041245014300055210006900198260001300267300001300280490000800293520127600301856005501577       2013                        eng d  a1477-912900aA truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development.0 atruncation allele in vascular endothelial growth factor c reveal  c2013 Apr  a1497-5060 v1403 a<p>Vascular endothelial growth factor C (Vegfc) is a secreted protein that guides lymphatic development in vertebrate embryos. However, its role during developmental angiogenesis is not well characterized. Here, we identify a mutation in zebrafish vegfc that severely affects lymphatic development and leads to angiogenesis defects on sensitized genetic backgrounds. The um18 mutation prematurely truncated Vegfc, blocking its secretion and paracrine activity but not its ability to activate its receptor Flt4. When expressed in endothelial cells, vegfc(um18) could not rescue lymphatic defects in mutant embryos, but induced ectopic blood vessel branching. Furthermore, vegfc-deficient endothelial cells did not efficiently contribute to tip cell positions in developing sprouts. Computational modeling together with assessment of endothelial cell dynamics by time-lapse analysis suggested that an autocrine Vegfc/Flt4 loop plays an important role in migratory persistence and filopodia stability during sprouting. Our results suggest that Vegfc acts in two distinct modes during development: as a paracrine factor secreted from arteries to guide closely associated lymphatic vasculature and as an autocrine factor to drive migratory persistence during angiogenesis.</p>  uhttps://www.jeltsch.org/Villefranc2013?language=fi01908nas a2200253   4500008004100000245007800041210006900119260001400188300001400202490000800216520113900224100002101363700002101384700002201405700002501427700002201452700002501474700002101499700002601520700001801546700001701564700002401581856004901605       2003                        eng d00aVEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia0 aVEGF guides angiogenic sprouting utilizing endothelial tip cell   c2003/Jun/  a1163 - 770 v1613 aVascular 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.1 aGerhardt, Holger1 aGolding, Matthew1 aFruttiger, Marcus1 aRuhrberg, Christiana1 aLundkvist, Andrea1 aAbramsson, Alexandra1 aJeltsch, Michael1 aMitchell, Christopher1 aAlitalo, Kari1 aShima, David1 aBetsholtz, Christer  uhttp://view.ncbi.nlm.nih.gov/pubmed/12810700