1. VEGF mediates commissural axon chemoattraction through its receptor Flk1.
- Author
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Ruiz de Almodovar C, Fabre PJ, Knevels E, Coulon C, Segura I, Haddick PC, Aerts L, Delattin N, Strasser G, Oh WJ, Lange C, Vinckier S, Haigh J, Fouquet C, Gu C, Alitalo K, Castellani V, Tessier-Lavigne M, Chedotal A, Charron F, and Carmeliet P
- Subjects
- Animals, Cells, Cultured, Chemotaxis genetics, Embryo, Mammalian, Enzyme-Linked Immunosorbent Assay methods, Glycoside Hydrolases metabolism, Growth Cones metabolism, Hedgehog Proteins metabolism, In Vitro Techniques, Mice, Mice, Transgenic, Nerve Growth Factors metabolism, Netrin-1, Neurons cytology, Rats, Rats, Sprague-Dawley, Rats, Wistar, Tumor Suppressor Proteins metabolism, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor Receptor-2 genetics, Wnt1 Protein genetics, Axons physiology, Chemotaxis physiology, Optic Chiasm cytology, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor Receptor-2 metabolism
- 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., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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