VEGF mediates commissural axon chemoattraction through its receptor Flk1.

VEGF mediates commissural axon chemoattraction through its receptor Flk1.
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DOI:
10.1016/j.neuron.2011.04.014
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发表时间:
2011-06-09
期刊:
影响因子:
16.2
通讯作者:
Carmeliet P
Carmeliet P
中科院分区:
医学1区
文献类型:
--
作者:
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;Carmeliet P

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Growing axons are guided to their targets by attractive and repulsive cues. In the developing spinal cord, Netrin-1 and Shh guide commissural axons towards the midline. However, the combined inhibition of their activity in commissural axon turning assays does not completely abrogate turning towards 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, while 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.
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