Genetic regulation of proliferation/differentiation characteristics of neural progenitor cells in the developing neocortex
Genetic regulation of proliferation/differentiation characteristics of neural progenitor cells in the developing neocortex
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DOI：
10.1016/j.braindev.2009.05.002
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发表时间：
2009-08-01
影响因子：
1.7
通讯作者：
Takahashi, Takao
中科院分区：
文献类型：
--
作者：
Mitsuhashi, Takayuki;Takahashi, Takao
不同哺乳动物的脑大小差异与脑功能的不同水平密切相关。调节神经元数量和大脑大小的机制必须至少部分嵌入在新皮层发育的非常早期阶段，即嵌入在新皮层神经祖细胞（NPC）的增殖/分化特征中。在这里，我们回顾了一系列的关键事件，通过这些事件，新皮层是在胚胎前脑形成的，特别强调产生非GABA能投射神经元的NPC的细胞周期动力学，大多数神经元在新皮层。一般而言，决定给定祖细胞群通过一系列细胞周期产生的细胞总数的关键参数是（1）构成产生期的细胞周期数和（2）每个细胞周期的祖细胞退出细胞周期的概率（Q分数或Q）。我们还将回顾调节上述关键参数的分子机制，特别是细胞周期G1期进展的细胞周期调节蛋白p27（Kipl）抑制剂。最后，作为神经元数量变化和Q分数改变导致的新皮质发育不全的例子，介绍了在p27（Kipl）缺失或过表达的小鼠中由遗传修饰引起的新皮质发育不全。(C)2009爱思唯尔有限公司版权所有。
Brain size variation among different mammals is tightly associated with different levels of cerebral function. Mechanisms that regulate the number of neurons and hence the size of the brain must be at least partially embedded within the very early phase of neocortical development, that is, embedded in proliferation/differentiation characteristics of the neural progenitor cells (NPCs) of the neocortex. Here we review a sequence of critical events through which the neocortex is formed in the embryonic forebrain, with particular emphasis on cell cycle kinetics of the NPCs that produce non-GABAergic projection neurons, the majority of neurons in the neocortex. In general, the critical parameters that determine the total number of cells produced by a given progenitor population through a sequence of cell cycles are (1) the number of cell cycles that constitute the production period and (2) the probability of cell cycle exit (Q fraction or Q) of progenitor cells for each of the cell cycles. We will also review molecular mechanisms that modulate the critical parameters above, with a special reference to the cell cycle regulatory protein p27(Kipl) inhibitor of G1 phase progression of the cell cycle. Finally the neocortical dysgenesis caused by genetic modification in mice where p27(Kipl) is either deleted or overexpressed is presented as examples of neuron number changes and resultant neocortical dysgenesis by Q fraction alteration. (C) 2009 Elsevier B.V. All rights reserved.