VEGF mediates commissural axon chemoattraction through its receptor Flk1

Neuron. 2011 Jun 9;70(5):966-78. doi: 10.1016/j.neuron.2011.04.014.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Axons / physiology*
  • Cells, Cultured
  • Chemotaxis / genetics
  • Chemotaxis / physiology*
  • 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
  • Optic Chiasm / cytology*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Tumor Suppressor Proteins / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • Wnt1 Protein / genetics

Substances

  • Hedgehog Proteins
  • Nerve Growth Factors
  • Ntn1 protein, mouse
  • Ntn1 protein, rat
  • Shh protein, mouse
  • Tumor Suppressor Proteins
  • Vascular Endothelial Growth Factor A
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • vascular endothelial growth factor A, mouse
  • Netrin-1
  • Vascular Endothelial Growth Factor Receptor-2
  • Glycoside Hydrolases
  • beta-galactanase