TY - JOUR T1 - Matrix-Binding Vascular Endothelial Growth Factor (VEGF) Isoforms Guide Granule Cell Migration in the Cerebellum via VEGF Receptor Flk1 JF - The Journal of Neuroscience JO - J. Neurosci. SP - 15052 LP - 15066 DO - 10.1523/JNEUROSCI.0477-10.2010 VL - 30 IS - 45 AU - Carmen Ruiz de Almodovar AU - Cathy Coulon AU - Paul Antoine Salin AU - Ellen Knevels AU - Naura Chounlamountri AU - Koen Poesen AU - Karlien Hermans AU - Diether Lambrechts AU - Katie Van Geyte AU - Joke Dhondt AU - Tom Dresselaers AU - Julie Renaud AU - Julian Aragones AU - Serena Zacchigna AU - Ilse Geudens AU - David Gall AU - Stijn Stroobants AU - Mireille Mutin AU - Karel Dassonville AU - Erik Storkebaum AU - Bénédicte F. Jordan AU - Ulf Eriksson AU - Lieve Moons AU - Rudi D'Hooge AU - Jody J. Haigh AU - Marie-Françoise Belin AU - Serge Schiffmann AU - Paul Van Hecke AU - Bernard Gallez AU - Stefan Vinckier AU - Alain Chédotal AU - Jérôme Honnorat AU - Nicole Thomasset AU - Peter Carmeliet AU - Claire Meissirel Y1 - 2010/11/10 UR - http://www.jneurosci.org/content/30/45/15052.abstract N2 - 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. ER -