The Outermost Region of the Developing Cortical Plate Is Crucial for Both the Switch of the Radial Migration Mode and the Dab1-Dependent "Inside-Out" Lamination in the Neocortex
The Outermost Region of the Developing Cortical Plate Is Crucial for Both the Switch of the Radial Migration Mode and the Dab1-Dependent "Inside-Out" Lamination in the Neocortex
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DOI：
10.1523/jneurosci.0650-11.2011
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发表时间：
2011-06-22
影响因子：
5.3
通讯作者：
Nakajima, Kazunori
中科院分区：
文献类型：
--
作者：
Sekine, Katsutoshi;Honda, Takao;Nakajima, Kazunori
哺乳动物的新皮层有一个层状结构，以出生日期为基础的“内向外”模式发育。这种层状结构是由神经元迁移建立的，迁移模式的顺序变化受几种信号级联调控，包括Reelin-Disabled homolog 1 （Dab1）通路。虽然“移动”这一主要迁移方式的重要性已经得到了很好的确立，但从移动到“终端易位”这一最终迁移方式的模式变化的生理意义尚不清楚。在本研究中，我们发现小鼠皮质板的最外层区域具有几个组织学上明显的特征，并将该区域命名为原始皮质带（PCZ）。延时分析显示，“运动”神经元在通过“终端易位”迁移到PCZ之前，会在PCZ下方短暂停留。此外，虽然dab1敲低（KD）神经元可以到达PCZ下方，但它们不能进入PCZ，这表明依赖dab1的末端易位是神经元进入PCZ的必要条件。重要的是，连续的子宫内电穿孔实验直接揭示了dab1依赖性末端易位的失败导致PCZ内由内到外排列的破坏，并且这种破坏模式在成熟皮层中仍然保留。相反，Dab1-KD运动神经元可以通过野生型和Dab1-KD前体在PCZ下传递。我们的数据表明，PCZ是一个独特的环境，神经元通过该环境涉及分子和行为上不同的迁移机制，并且在PCZ下方从运动到终端易位的迁移模式变化对于成熟皮层中依赖dab1的内向外层压至关重要。
Mammalian neocortex has a laminated structure that develops in a birth-date-dependent "inside-out" pattern. This layered structure is established by neuronal migration with sequential changes of the migratory mode regulated by several signaling cascades, including the Reelin-Disabled homolog 1 (Dab1) pathway. Although the importance of "locomotion," the major migratory mode, has been well established, the physiological significance of the mode change from locomotion to "terminal translocation," the final migratory mode, is unknown. In this study, we found that the outermost region of the mouse cortical plate has several histologically distinct features and named this region the primitive cortical zone (PCZ). Time-lapse analyses revealed that "locomoting" neurons paused transiently just beneath the PCZ before migrating into it by "terminal translocation." Furthermore, whereas Dab1-knockdown (KD) neurons could reach beneath the PCZ, they failed to enter the PCZ, suggesting that the Dab1-dependent terminal translocation is necessary for entry of the neurons into the PCZ. Importantly, sequential in utero electroporation experiments directly revealed that failure of the Dab1-dependent terminal translocation resulted in disruption of the inside-out alignment within the PCZ and that this disrupted pattern was still preserved in the mature cortex. Conversely, Dab1-KD locomoting neurons could pass by both wild-type and Dab1-KD predecessors beneath the PCZ. Our data indicate that the PCZ is a unique environment, passage of neurons through which involves molecularly and behaviorally different migratory mechanisms, and that the migratory mode change from locomotion to terminal translocation just beneath the PCZ is critical for the Dab1-dependent inside-out lamination in the mature cortex.