VEGFR2 (KDR/Flk1) Signaling Mediates Axon Growth in Response to Semaphorin 3E in the Developing Brain
VEGFR2 (KDR/Flk1) Signaling Mediates Axon Growth in Response to Semaphorin 3E in the Developing Brain
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DOI：
10.1016/j.neuron.2010.04.006
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发表时间：
2010-04-29
期刊：
影响因子：
16.2
通讯作者：
Mann, Fanny
中科院分区：
文献类型：
--
作者：
Bellon, Anais;Luchino, Jonathan;Mann, Fanny
共同的因素被认为是控制血管和神经元模式。在这里，我们报告了在小鼠大脑轴突束形成中血管内皮生长因子受体2型（VEGFR 2）的体内需求。我们发现，VEGFR 2表达的神经元的下托和介导轴突伸长的脑信号蛋白（Sema）家族分子，Sema 3E。我们进一步表明，VEGFR 2与丛蛋白D1/神经纤毛蛋白-1（Nrp 1）受体复合物的Sema 3E和成为酪氨酸磷酸化Sema 3E刺激。在下托神经元中，Sema 3E触发VEGFR 2依赖性的磷脂酰肌醇-3激酶（PI 3 K）/Akt通路的激活，这是轴突生长增加所必需的。这些结果暗示VEGFR 2通过依赖于Sema 3E和独立于血管内皮生长因子（VEGF）配体的机制参与轴突布线。这一机制解释了脑信号蛋白如何激活发育中神经元的轴突生长促进反应。
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.