Role of Sox2 in the development of the mouse neocortex
Role of Sox2 in the development of the mouse neocortex
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DOI：
10.1016/j.ydbio.2006.03.007
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发表时间：
2006-07-01
影响因子：
2.7
通讯作者：
Sikorska, Marianna
中科院分区：
文献类型：
--
作者：
Bani-Yaghoub, Mahmud;Tremblay, Roger G.;Sikorska, Marianna
哺乳动物的新皮质由神经干细胞和祖细胞形成，这些细胞利用特定的转录因子和环境因素来产生功能性神经元和星形胶质细胞。在此，我们研究了Sox2在新皮质神经发生和胶质发生过程中的作用机制。我们发现室管膜区的神经干细胞和祖细胞中存在稳定的Sox2表达，这种表达一直持续到细胞退出细胞周期。在神经祖细胞中过表达组成型活性Sox2会导致Notch1、重组信号序列结合蛋白 - J（RBP - J）和分裂增强子相关蛋白5（Hes5）转录本上调，并且Sox2的高迁移率族（HMG）结构域似乎足以产生这些效应。虽然Sox2过表达允许祖细胞分化为星形胶质细胞，但它会抑制神经发生，除非Notch通路被阻断。此外，神经元前体利用一种或多种丝氨酸蛋白酶来消除过表达的Sox2蛋白，从而解除对神经发生的抑制。另一方面，胶质前体和分化的星形胶质细胞会维持Sox2表达，直到它们进入静止状态。触发星形胶质细胞增殖的信号（即损伤、有丝分裂原和胶质生成因子）会重新激活Sox2表达。综上所述，Sox2似乎在Notch信号通路上游发挥作用，以维持细胞的增殖潜能，并确保在发育中的新皮质产生足够数量和表型的细胞。版权所有（c）2006，爱思唯尔公司出版。保留所有权利。
The mammalian neocortex is established from neural stem and progenitor cells that utilize specific transcriptional and environmental factors to create functional neurons and astrocytes. Here, we examined the mechanism of Sox2 action during neocortical neurogenesis and gliogenesis. We established a robust Sox2 expression in neural stem and progenitor cells within the ventricular zone, which persisted until the cells exited the cell cycle. Overexpression of constitutively active Sox2 in neural progenitors resulted in upregulation of Notch1, recombination signal-sequence binding protein-J (RBP-J) and hairy enhancer of split 5 (Hes5) transcripts and the Sox2 high mobility group (HMG) domain seemed sufficient to confer these effects. While Sox2 overexpression permitted the differentiation of progenitors into astroglia, it inhibited neurogenesis, unless the Notch pathway was blocked. Moreover, neuronal precursors engaged a serine protease(s) to eliminate the overexpressed Sox2 protein and relieve the repression of neurogenesis. Glial precursors and differentiated astrocytes, on the other hand, maintained Sox2 expression until they reached a quiescent state. Sox2 expression was re-activated by signals that triggered astrocytic proliferation (i.e., injury, mitogenic and gliogenic factors). Taken together, Sox2 appears to act upstream of the Notch signaling pathway to maintain the cell proliferative potential and to ensure the generation of sufficient cell numbers and phenotypes in the developing neocortex. Crown Copyright (c) 2006 Published by Elsevier Inc. All rights reserved.