VEGFR2 (KDR/Flk1) Signaling Mediates Axon Growth in Response to Semaphorin 3E in the Developing Brain

被引：117

作者：

Bellon, Anais ^{[1
]}

Luchino, Jonathan ^{[1
]}

Haigh, Katharina ^{[2
,3
]}

Rougon, Genevieve ^{[1
]}

Haigh, Jody ^{[2
,3
]}

Chauvet, Sophie ^{[1
]}

Mann, Fanny ^{[1
]}

机构：

[1] Univ Aix Marseille 2, CNRS, UMR 6216, Dev Biol Inst Marseille Luminy, F-13288 Marseille 09, France

[2] Univ Ghent VIB, Vasc Cell Biol Unit, Dept Mol Biomed Res, B-9000 Ghent, Belgium

[3] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium

来源：

NEURON | 2010年 / 66卷 / 02期

关键词：

ENDOTHELIAL-CELLS; NERVOUS-SYSTEM; NEURAL PROGENITORS; ADAPTER PROTEIN; RECEPTOR; RAT; NEUROPILIN-1; PROJECTIONS; ACTIVATION; MIGRATION;

D O I：

10.1016/j.neuron.2010.04.006

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Common factors are thought to control vascular and neuronal patterning. Here we report an in vivo requirement for the vascular endothelial growth factor receptor type 2 (VEGFR2) in axon tract formation in the mouse brain. We show that VEGFR2 is expressed by neurons of the subiculum and mediates axonal elongation in response to the semaphorin (Sema) family molecule, Sema3E. We further show that VEGFR2 associates with the PlexinD1/Neuropilin-1 (Nrp1) receptor complex for Sema3E and becomes tyrosine-phosphorylated upon Sema3E stimulation. In subicular neurons, Sema3E triggers VEGFR2-dependent activation of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway that is required for the increase in axonal growth. These results implicate VEGFR2 in axonal wiring through a mechanism dependent on Sema3E and independent of vascular endothelial growth factor (VEGF) ligands. This mechanism provides an explanation as to how a semaphorin can activate an axon growth promoting response in developing neurons.

引用

页码：205 / 219

页数：15

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