Regionalization of developing brain and neuronal migration

神经元迁移对于构建神经元的层和核等结构是至关重要的。本研究进行了一项系统的分析，以检验来自皮质VZ的皮质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)编码的质粒通过宫内电穿孔的方法标记小鼠胚胎的VZ细胞，并在适当的存活时间后对标记的细胞进行评估。在胚胎12.5天或E15.5天进行电穿孔后，GFP VZ细胞最初呈纺锤形，呈放射状。离开VZ后，它们转化为圆形或水平定向的梭形神经元，具有许多短突起。然后，当它们向上移动时，它们似乎逐渐变成了放射状的双极细胞。而标记在E12.5(早期出生神经元)的VZ细胞在这些变化后最早到达皮质板(CP)的顶端，而标记在E15.5(晚出生的神经元)的VZ细胞则进一步沿着放射状纤维的长度迁移到CP的顶端。然后将一个显性阴性形式的细胞周期蛋白依赖性激酶5基因(Cdk5dN)导入VZ细胞。将cdk5dn基因导入E12.5VZ细胞，并不影响早期神经元的迁移。然而，这导致晚出生的神经元迁移失败，尽管它们在中间带转变为双极形状。因此，皮质神经元似乎至少有两个不同的迁移阶段：一个是出生较早和较晚出生的神经元共有的，另一个是出生较晚的神经元和依赖CDK5的神经元所特有的。

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.