GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège, 4000, Belgium.
Adv Exp Med Biol. 2014;800:59-74. doi: 10.1007/978-94-007-7687-6_4.
The cerebral cortex is one of the most intricate regions of the brain, which required elaborated cell migration patterns for its development. Experimental observations show that projection neurons migrate radially within the cortical wall, whereas interneurons migrate along multiple tangential paths to reach the developing cortex. Tight regulation of the cell migration processes ensures proper positioning and functional integration of neurons to specific cerebral cortical circuits. Disruption of neuronal migration often lead to cortical dysfunction and/or malformation associated with neurological disorders. Unveiling the molecular control of neuronal migration is thus fundamental to understand the physiological or pathological development of the cerebral cortex. Generation of functional cortical neurons is a complex and stratified process that relies on decision of neural progenitors to leave the cell cycle and generate neurons that migrate and differentiate to reach their final position in the cortical wall. Although accumulating work shed some light on the molecular control of neuronal migration, we currently do not have a comprehensive understanding of how cell cycle exit and migration/differentiation are coordinated at the molecular level. The current chapter tends to lift the veil on this issue by discussing how core cell cycle regulators, and in particular p27(Kip1) acts as a multifunctional protein to control critical steps of neuronal migration through activities that go far beyond cell cycle regulation.
大脑皮层是大脑中最复杂的区域之一，其发育需要精细的细胞迁移模式。实验观察表明，投射神经元在皮层壁内放射状迁移，而中间神经元则沿着多个切线路径迁移，到达发育中的皮层。细胞迁移过程的严格调控确保了神经元在特定大脑皮层回路中的正确定位和功能整合。神经元迁移的破坏常常导致与神经障碍相关的皮层功能障碍和/或畸形。因此，揭示神经元迁移的分子调控对于理解大脑皮层的生理或病理发育至关重要。功能性皮质神经元的产生是一个复杂的分层过程，依赖于神经祖细胞离开细胞周期并产生迁移和分化以到达皮层壁中最终位置的神经元的决定。尽管越来越多的工作揭示了神经元迁移的分子调控，但我们目前还没有全面了解细胞周期退出和迁移/分化如何在分子水平上协调。本章旨在通过讨论核心细胞周期调节剂，特别是 p27(Kip1) 如何作为一种多功能蛋白通过超越细胞周期调控的活动来控制神经元迁移的关键步骤，来揭开这个问题的面纱。
