VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1

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• 作者：Carmen Ruiz  ; de  ; Almodovar¹ ; ² ; ¹⁶ ; Pierre  ; J. Fabre³ ; ¹⁶ ; Ellen Knevels¹ ; ² ; Cathy Coulon¹ ; ² ; Inmaculada Segura¹ ; ² ; Patrick  ; C.G. Haddick⁴ ; Liesbeth Aerts¹ ; ² ; Nicolas Delattin¹ ; ² ; Geraldine Strasser⁴ ; Won-Jong Oh⁵ ; Christian Lange¹ ; ² ; Stefan Vinckier¹ ; ² ; Jody Haigh⁶ ; ⁷ ; Coralie Fouquet⁸ ; Chengua Gu⁵ ; Kari Alitalo⁹ ; ¹⁰ ; ¹¹ ; ¹² ; Valerie Castellani¹³ ; Marc Tessier-Lavigne⁴ ; Alain Chedotal¹⁴ ; Frederic Charron³ ; ¹⁵ ; ^{frederic.charron@ircm.qc.ca"" rel=""nofollow} ; Peter Carmeliet¹ ; ² ; ^{peter.carmeliet@vib-kuleuven.be"" rel=""nofollow}
• 刊名：Neuron
• 出版年：2011
• 出版时间：9 June 2011
• 年：2011
• 卷：70
• 期：5
• 页码：966-978
• 全文大小：2008 K

文摘

Summary

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.