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Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1

(2010) JOURNAL OF NEUROSCIENCE. 30(45). p.15052-15066
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Abstract
Vascular endothelial growth factor (VEGF) regulates angiogenesis, but also has important, yet poorly characterized roles in neuronal wiring. Using several genetic and in vitro approaches, we discovered a novel role for VEGF in the control of cerebellar granule cell (GC) migration from the external granule cell layer (EGL) toward the Purkinje cell layer (PCL). GCs express the VEGF receptor Flk1, and are chemoattracted by VEGF, whose levels are higher in the PCL than EGL. Lowering VEGF levels in mice in vivo or ectopic VEGF expression in the EGL ex vivo perturbs GC migration. Using GC-specific Flk1 knock-out mice, we provide for the first time in vivo evidence for a direct chemoattractive effect of VEGF on neurons via Flk1 signaling. Finally, using knock-in mice expressing single VEGF isoforms, we show that pericellular deposition of matrix-bound VEGF isoforms around PC dendrites is necessary for proper GC migration in vivo. These findings identify a previously unknown role for VEGF in neuronal migration
Keywords
NEURONAL MIGRATION, NERVOUS-SYSTEM, STIMULATES AXONAL OUTGROWTH, NEUROTROPHIC FACTOR, GENE-EXPRESSION, BERGMANN GLIA, MICE LACKING, FACIAL-NERVE, IN-VITRO, ANGIOGENESIS

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Citation

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Chicago
de Almodovar, Carmen Ruiz, Cathy Coulon, Paul Antoine Salin, Ellen Knevels, Naura Chounlamountri, Koen Poesen, Karlien Hermans, et al. 2010. “Matrix-binding Vascular Endothelial Growth Factor (VEGF) Isoforms Guide Granule Cell Migration in the Cerebellum via VEGF Receptor Flk1.” Journal of Neuroscience 30 (45): 15052–15066.
APA
de Almodovar, C. R., Coulon, C., Salin, P. A., Knevels, E., Chounlamountri, N., Poesen, K., Hermans, K., et al. (2010). Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1. JOURNAL OF NEUROSCIENCE, 30(45), 15052–15066.
Vancouver
1.
de Almodovar CR, Coulon C, Salin PA, Knevels E, Chounlamountri N, Poesen K, et al. Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1. JOURNAL OF NEUROSCIENCE. 2010;30(45):15052–66.
MLA
de Almodovar, Carmen Ruiz, Cathy Coulon, Paul Antoine Salin, et al. “Matrix-binding Vascular Endothelial Growth Factor (VEGF) Isoforms Guide Granule Cell Migration in the Cerebellum via VEGF Receptor Flk1.” JOURNAL OF NEUROSCIENCE 30.45 (2010): 15052–15066. Print.
@article{1082061,
  abstract     = {Vascular endothelial growth factor (VEGF) regulates angiogenesis, but also has important, yet poorly characterized roles in neuronal wiring. Using several genetic and in vitro approaches, we discovered a novel role for VEGF in the control of cerebellar granule cell (GC) migration from the external granule cell layer (EGL) toward the Purkinje cell layer (PCL). GCs express the VEGF receptor Flk1, and are chemoattracted by VEGF, whose levels are higher in the PCL than EGL. Lowering VEGF levels in mice in vivo or ectopic VEGF expression in the EGL ex vivo perturbs GC migration. Using GC-specific Flk1 knock-out mice, we provide for the first time in vivo evidence for a direct chemoattractive effect of VEGF on neurons via Flk1 signaling. Finally, using knock-in mice expressing single VEGF isoforms, we show that pericellular deposition of matrix-bound VEGF isoforms around PC dendrites is necessary for proper GC migration in vivo. These findings identify a previously unknown role for VEGF in neuronal migration},
  author       = {de Almodovar, Carmen Ruiz and Coulon, Cathy and Salin, Paul Antoine and Knevels, Ellen and Chounlamountri, Naura and Poesen, Koen and Hermans, Karlien and Lambrechts, Diether and Van Geyte, Katie and Dhondt, Joke and Dresselaers, Tom and Renaud, Julie and Aragones, Julian and Zacchigna, Serena and Geudens, Ilse and Gall, David and Stroobants, Stijn and Mutin, Mireille and Dassonville, Karel and Storkebaum, Erik and Jordan, Benedicte F and Eriksson, Ulf and Moons, Lieve and D'Hooge, Rudi and Haigh, Jody and Belin, Marie-Francoise and Schiffmann, Serge and Van Hecke, Paul and Gallez, Bernard and Vinckier, Stefan and Chedotal, Alain and Honnorat, Jerome and Thomasset, Nicole and Carmeliet, Peter and Meissirel, Claire},
  issn         = {0270-6474},
  journal      = {JOURNAL OF NEUROSCIENCE},
  keyword      = {NEURONAL MIGRATION,NERVOUS-SYSTEM,STIMULATES AXONAL OUTGROWTH,NEUROTROPHIC FACTOR,GENE-EXPRESSION,BERGMANN GLIA,MICE LACKING,FACIAL-NERVE,IN-VITRO,ANGIOGENESIS},
  language     = {eng},
  number       = {45},
  pages        = {15052--15066},
  title        = {Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.0477-10.2010},
  volume       = {30},
  year         = {2010},
}

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