title: VEGF mediates commissural axon chemoattraction through its receptor Flk1.
abstract: Growing axons are guided to their targets by attractive and repulsive cues. In the developing spinal cord, Netrin-1 and Shh guide commissural axons toward the midline. However, the combined inhibition of their activity in commissural axon turning assays does not completely abrogate turning toward floor plate tissue, suggesting that additional guidance cues are present. Here we show that the prototypic angiogenic factor VEGF is secreted by the floor plate and is a chemoattractant for commissural axons in vitro and in vivo. Inactivation of Vegf in the floor plate or of its receptor Flk1 in commissural neurons causes axon guidance defects, whereas Flk1 blockade inhibits turning of axons to VEGF in vitro. Similar to Shh and Netrin-1, VEGF-mediated commissural axon guidance requires the activity of Src family kinases. Our results identify VEGF and Flk1 as a novel ligand/receptor pair controlling commissural axon guidance.
authors.affiliation: VIB, Laboratory for Angiogenesis and the Neurovascular link, Vesalius Research Center, KULeuven, Leuven, Belgium.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ruiz de Almodovar
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Fabre
authors.forename: Ellen
authors.initials: E
authors.lastname: Knevels
authors.forename: Cathy
authors.initials: C
authors.lastname: Coulon
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Segura
authors.forename: Patrick C G
authors.initials: PC
authors.lastname: Haddick
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Aerts
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delattin
authors.forename: Geraldine
authors.initials: G
authors.lastname: Strasser
authors.forename: Won-Jong
authors.initials: WJ
authors.lastname: Oh
authors.forename: Christian
authors.initials: C
authors.lastname: Lange
authors.forename: Stefan
authors.initials: S
authors.lastname: Vinckier
authors.forename: Jody
authors.initials: J
authors.lastname: Haigh
authors.forename: Coralie
authors.initials: C
authors.lastname: Fouquet
authors.forename: Chengua
authors.initials: C
authors.lastname: Gu
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Valerie
authors.initials: V
authors.lastname: Castellani
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.forename: Alain
authors.initials: A
authors.lastname: Chedotal
authors.forename: Frederic
authors.initials: F
authors.lastname: Charron
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006026:Glycoside Hydrolases / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000378:metabolism; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology; D009897:Optic Chiasm / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*; D051155:Wnt1 Protein / Q000235:genetics
chemical_list: D053823:Hedgehog Proteins; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; C465570:Shh protein, mouse; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C467480:vascular endothelial growth factor A, mouse; D000075388:Netrin-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D006026:Glycoside Hydrolases; C089138:beta-galactanase