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 Charron; Peter Carmeliet

doi:10.1016/j.neuron.2011.04.014

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 journal › Article › Research › peer-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 language	English
Pages (from-to)	966-978
Number of pages	13
Journal	Neuron
Volume	70
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2011.04.014
Publication status	Published - 9 Jun 2011
Externally published	Yes

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10.1016/j.neuron.2011.04.014

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Cite this

Ruiz de Almodovar, C., Fabre, P. J., Knevels, E., Coulon, C., Segura, I., Haddick, P. C. G., Aerts, L., Delattin, N., Strasser, G., Oh, W. J., Lange, C., Vinckier, S., Haigh, J., Fouquet, C., Gu, C., Alitalo, K., Castellani, V., Tessier-Lavigne, M., Chedotal, A., ... Carmeliet, P. (2011). VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1. Neuron, 70(5), 966-978. https://doi.org/10.1016/j.neuron.2011.04.014

Ruiz de Almodovar, Carmen ; Fabre, Pierre J. ; Knevels, Ellen ; Coulon, Cathy ; Segura, Inmaculada ; Haddick, Patrick C G ; Aerts, Liesbeth ; Delattin, Nicolas ; Strasser, Geraldine ; Oh, Won Jong ; Lange, Christian ; Vinckier, Stefan ; Haigh, Jody ; Fouquet, Coralie ; Gu, Chengua ; Alitalo, Kari ; Castellani, Valerie ; Tessier-Lavigne, Marc ; Chedotal, Alain ; Charron, Frederic ; Carmeliet, Peter. / VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1. In: Neuron. 2011 ; Vol. 70, No. 5. pp. 966-978.

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title = "VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1",

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. {\textcopyright} 2011 Elsevier Inc.",

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

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Ruiz de Almodovar, C, Fabre, PJ, Knevels, E, Coulon, C, Segura, I, Haddick, PCG, 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 2011, 'VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1', Neuron, vol. 70, no. 5, pp. 966-978. https://doi.org/10.1016/j.neuron.2011.04.014

VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1. / Ruiz de Almodovar, Carmen; Fabre, Pierre J.; Knevels, Ellen; Coulon, Cathy; Segura, Inmaculada; Haddick, Patrick C G; Aerts, Liesbeth; Delattin, Nicolas; Strasser, Geraldine; Oh, Won Jong; Lange, Christian; Vinckier, Stefan; Haigh, Jody; Fouquet, Coralie; Gu, Chengua; Alitalo, Kari; Castellani, Valerie; Tessier-Lavigne, Marc; Chedotal, Alain; Charron, Frederic; Carmeliet, Peter.

In: Neuron, Vol. 70, No. 5, 09.06.2011, p. 966-978.

Research output: Contribution to journal › Article › Research › peer-review

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AU - Ruiz de Almodovar, Carmen

AU - Fabre, Pierre J.

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AU - Segura, Inmaculada

AU - Haddick, Patrick C G

AU - Aerts, Liesbeth

AU - Delattin, Nicolas

AU - Strasser, Geraldine

AU - Oh, Won Jong

AU - Lange, Christian

AU - Vinckier, Stefan

AU - Haigh, Jody

AU - Fouquet, Coralie

AU - Gu, Chengua

AU - Alitalo, Kari

AU - Castellani, Valerie

AU - Tessier-Lavigne, Marc

AU - Chedotal, Alain

AU - Charron, Frederic

AU - Carmeliet, Peter

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AB - 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.

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