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Title: Robo3在皮层神经元放射状迁移中的作用
Author: 司马健
Degree Level: 博士
Issued Date: 2009-03-20
Degree Grantor: 中国科学院上海生命科学研究院
Place of Degree Grantor: 上海生命科学研究院
Supervisor: 袁小兵
Keyword: 放射状迁移 ; 轴突导向 ; Slit ; Robo3 ; 大脑皮层
Alternative Title: The role of Robo3 in Radial Migration of cortical neurons
Major: 神经生物学
Abstract: 在哺乳动物大脑皮层的发育过程中,为建立复杂的神经突触连接,新生的神经元从脑室区(ventricular zone,VZ)向皮层板(cortical plate,CP)做放射状迁移,到达最外层后便停止迁移并进行树突发育。控制这种发育过程的时空调节信号目前尚不清楚。在本研究中,我们发现Slit受体家族成员 Robo3 的表达对于神经元迁移进入皮层板是必需的。当用 siRNA 的方法敲减 Robo3(而非Robo2)的表达后,神经元进入皮层板的过程受到了阻断。然而,当同时敲减 Robo3 和 Robo2 表达时,这种迁移的缺陷又消失了,这一现象提示了 Robo3 下调引起的迁移缺陷是 Robo2 依赖的。离体组织块培养以及单细胞培养的实验又进一步表明,那些 Robo3 表达水平下调的神经元展现了一种 slit 诱导的突起排斥或收缩,而这一现象与在体一样是 Robo2 依赖的。所以,Robo3 分子的功能是通过抑制 Robo2 介导的排斥作用而帮助神经元顺利的从 VZ 向 CP 进行放射状迁移。
English Abstract: Newborn cortical neurons undergo radial migration from the ventricular zone (VZ) toward the surface of the cortical plate (CP) during the morphogenesis of cerebral cortex. The spatial-temporal signals that control this stereotyped radial migration remain elusive. Here we report that in developing rat cortex, expression of the Slit receptor family member Robo3 in newborn neurons is essential for these neurons to migrate into the CP. We found that the CP entry was prevented when Robo3 but not Robo2 expression was down-regulated by specific siRNAs. This migration defect was conquered when both Robo3 and Robo2 were simultaneously down-regulated, suggesting the emergence of a Robo2-dependent migration retardation in the absence of Robo3 in these neurons. Moreover, cultured cortical neurons with reduced Robo3 expression showed Slit-induced neurite retraction and repulsive migration away from co-cultured Slit-secreting cell aggregates only when Robo2 was present in the neurons. Thus, Robo3 may allow the radially migrating neurons to invade the CP by suppressing Robo2-mediated repulsion in response to CP-derived Slit1.
Language: 中文
Content Type: 学位论文
URI: http://ir.sibs.ac.cn/handle/331001/2404
Appears in Collections:神经所(总)_学位论文

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Recommended Citation:
Robo3在皮层神经元放射状迁移中的作用.司马健[d].中国科学院上海生命科学研究院,2009.20-25
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