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Regionalization of developing brain and neuronal migration

发育中的大脑和神经元迁移的区域化

基本信息

批准号：
14208095
负责人：
MURAKAMI Fujio
金额：
$ 34.03万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Neuronal migration is crucial for the construction of neuronal architecture such as layers and nuclei. The present study carried out a systematic analysis to examine whether the migratory behavior of cortical neurons derived from the cortical VZ is stage-dependent. We labeled VZ cells of mouse embryos with green fluorescent protein(gfp)-encoding plasmids by in utero electroporation and evaluated the labeled cells after appropriate survival periods. After electroporation at either embryonic day (E) 12.5 or E15.5, GFP+VZ cells were initially spindle-shaped and radially oriented. After leaving the VZ, they transformed into round or horizontally oriented fusiform neurons with many short processes. They then seemed to gradually change into radially oriented bipolar cells as they moved upward. Whereas the earliest emigrants from the VZ labeled at E12.5(early-born neurons) reached the top of the cortical plate(CP) after these changes, VZ cells labeled at E15.5(late-born neurons) further migrated along the length of radial fibers to reach the top of the CP. A dominant negative form of the gene for cyclin-dependent kinase 5(Cdk5DN) was then introduced into VZ cells. Transfection of E12.5 VZ with cdk5dn did not disrupt the migration of the early-born neurons. However, this caused a failure in migration of the late-born neurons, although they transformed into bipolar shapes in the intermediate zone. Thus, there appear to be at least two distinct migratory phases of cortical neurons : one common to the early- and late-born neurons, and the other specific to late-born neurons and Cdk5-dependent.

神经元迁移对于神经元结构如层和核的构建至关重要。本研究系统分析了皮层VZ区神经元的迁移行为是否具有阶段依赖性。我们用绿色荧光蛋白（gfp）编码质粒标记的小鼠胚胎VZ细胞在子宫内电穿孔，并评估标记的细胞后，适当的生存期。在胚胎第12.5或E15.5天电穿孔后，GFP+VZ细胞最初呈纺锤形并呈放射状取向。离开VZ后，它们转化为圆形或水平取向的梭形神经元，具有许多短突起。然后，他们似乎逐渐变成放射状定向双极细胞，因为他们向上移动。而最早的移民从VZ标记在E12.5（早期出生的神经元）到达顶部的皮质板（CP）后，这些变化，VZ细胞标记在E15.5（晚出生的神经元）进一步迁移沿着长度的径向纤维到达CP的顶部。然后将细胞周期蛋白依赖性激酶5（Cdk5DN）基因的显性负性形式引入VZ细胞。用cdk5dn转染E12.5 VZ并不破坏早期出生的神经元的迁移。然而，这导致晚生神经元迁移失败，尽管它们在中间区转化为双极形状。因此，似乎有至少两个不同的迁移阶段的皮层神经元：一个共同的早期和晚期出生的神经元，和其他特定的晚期出生的神经元和Cdk5依赖。