Control of cortical interneuron migration by neurotrophins and PI3-kinase signaling.
Control of cortical interneuron migration by neurotrophins and PI3-kinase signaling.
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发表时间：
2002-07
期刊：
影响因子：
4.6
通讯作者：
F. Polleux;Kristin L. Whitford;P. Dijkhuizen;T. Vitalis;Anirvan Ghosh
中科院分区：
文献类型：
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作者：
F. Polleux;Kristin L. Whitford;P. Dijkhuizen;T. Vitalis;Anirvan Ghosh
在端脑发育过程中，来自内侧神经节隆起（MGE）的细胞被认为迁移到新皮质，产生大多数皮质GABA能中间神经元。通过结合延时视频显微镜，免疫荧光和药理学扰动在一个新的体外迁移试验，我们发现，MGE衍生的细胞迁移通过整个程度的皮质和海马CA领域，但避免齿状回。迁移神经元最初在边缘区和中间区内行进，并且可以从任一位置进入皮质板。切向迁移强烈刺激BDNF和NT 4和衰减的Trk家族抑制剂，K252 a，表明迁移是由TrkB信号调节。此外，TrkB基因敲除小鼠显示胚胎皮质中切向迁移的钙结合蛋白阳性神经元的数量显著减少。BDNF和NT 4引起MGE细胞中PI 3-激酶的快速激活，并且抑制PI 3-激酶（但不抑制MAP激酶或PLC γ）显著减弱切向迁移。这些观察结果表明，TrkB信号，通过PI 3-激酶激活，在控制发育中的大脑皮层的神经元间迁移中起着重要的作用。
During telencephalic development, cells from the medial ganglionic eminence (MGE) are thought to migrate to the neocortex to give rise to a majority of cortical GABAergic interneurons. By combining time-lapse video-microscopy, immunofluorescence and pharmacological perturbations in a new in vitro migration assay, we find that MGE-derived cells migrate through the entire extent of the cortex and into the CA fields of the hippocampus, but avoid the dentate gyrus. Migrating neurons initially travel within the marginal zone and intermediate zone, and can enter the cortical plate from either location. Tangential migration is strongly stimulated by BDNF and NT4 and attenuated by the Trk-family inhibitor, K252a, suggesting that migration is regulated by TrkB signaling. Furthermore, TrkB-null mice show a significant decrease in the number of calbindin-positive neurons migrating tangentially in the embryonic cortex. BDNF and NT4 cause rapid activation of PI3-kinase in MGE cells, and inhibition of PI3-kinase (but not of MAP kinase or PLCgamma) dramatically attenuates tangential migration. These observations suggest that TrkB signaling, via PI3-kinase activation, plays an important role in controlling interneuron migration in the developing cerebral cortex.