VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1

Carmen Ruiz de Almodovar, Pierre J. Fabre, Ellen Knevels, Cathy Coulon, Inmaculada Segura, Patrick C G Haddick, Liesbeth Aerts, Nicolas Delattin, Geraldine Strasser, Won Jong Oh, Christian Lange, Stefan Vinckier, Jody Haigh, Coralie Fouquet, Chengua Gu, Kari Alitalo, Valerie Castellani, Marc Tessier-Lavigne, Alain Chedotal, Frederic CharronPeter Carmeliet

Research output: Contribution to journalArticleResearchpeer-review

102 Citations (Scopus)

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. © 2011 Elsevier Inc.

Original languageEnglish
Pages (from-to)966-978
Number of pages13
JournalNeuron
Volume70
Issue number5
DOIs
Publication statusPublished - 9 Jun 2011
Externally publishedYes

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