Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, Japan.
Cereb Cortex. 2019 Aug 14;29(9):3725-3737. doi: 10.1093/cercor/bhy252.
The development of the mammalian cerebral cortex involves a variety of temporally organized events such as successive waves of neuronal production and the transition of progenitor competence for each neuronal subtype generated. The number of neurons generated in a certain time period, that is, the rate of neuron production, varies across the regions of the brain and the specific developmental stage; however, the underlying mechanism of this process is poorly understood. We have recently found that nascent neurons communicate with undifferentiated progenitors and thereby regulate neurogenesis, through a transiently retained apical endfoot that signals via the Notch pathway. Here, we report that the retention time length of the neuronal apical endfoot correlates with the rate of neuronal production in the developing mouse cerebral cortex. We further demonstrate that a forced reduction or extension of the retention period through the disruption or stabilization of adherens junction, respectively, resulted in the acceleration or deceleration of neurogenesis, respectively. Our results suggest that the apical endfeet of differentiating cells serve as a pace controller for neurogenesis, thereby assuring the well-proportioned laminar organization of the neocortex.
哺乳动物大脑皮层的发育涉及多种时间组织的事件，例如神经元产生的连续波和产生的每个神经元亚型的祖细胞能力的转变。在特定时间段内产生的神经元数量，即神经元产生的速度，在大脑区域和特定发育阶段之间有所不同；然而，这个过程的潜在机制还了解甚少。我们最近发现，通过暂存的顶端足突，新生神经元与未分化的祖细胞进行通讯，并通过 Notch 途径发出信号，从而调节神经发生。在这里，我们报告说，神经元顶端足突的保留时间长度与发育中的小鼠大脑皮层的神经元产生速度相关。我们进一步证明，通过破坏或稳定黏着连接分别减少或延长保留期，分别导致神经发生的加速或减速。我们的结果表明，分化细胞的顶端足突作为神经发生的起搏控制器，从而确保新皮层的层状组织得到良好的比例。
