Genetic ablation of Rest leads to in vitro-specific derepression of neuronal genes during neurogenesis
Genetic ablation of Rest leads to in vitro-specific derepression of neuronal genes during neurogenesis
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DOI：
10.1242/dev.072272
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发表时间：
2012-02-15
期刊：
影响因子：
4.6
通讯作者：
Yamada, Yasuhiro
中科院分区：
文献类型：
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作者：
Aoki, Hitomi;Hara, Akira;Yamada, Yasuhiro
REST(Re1沉默转录因子，又称Nrsf)通过阻止神经元基因的早熟表达，在体外参与维持神经干/祖细胞的未分化状态。然而，由于常规REST基因敲除小鼠的早期胚胎致死表型，REST在体内神经发生过程中的作用仍有待阐明。在目前的研究中，我们产生了REST条件性基因敲除小鼠，它允许在体内检测胚胎神经发生过程中REST基因消融的效果。我们发现，REST在体外培养的神经细胞和中枢神经系统外的非神经细胞中都具有抑制神经基因表达的作用，但对于体内胚胎神经发生来说，REST是必不可少的。我们的发现强调了在活体胚胎神经发生过程中，外在信号对于适当的内在调节神经元基因表达水平的重要性，在指定细胞命运方面。
Rest (RE1-silencing transcription factor, also called Nrsf) is involved in the maintenance of the undifferentiated state of neuronal stem/progenitor cells in vitro by preventing precocious expression of neuronal genes. However, the function of Rest during neurogenesis in vivo remains to be elucidated because of the early embryonic lethal phenotype of conventional Rest knockout mice. In the present study, we have generated Rest conditional knockout mice, which allow the effect of genetic ablation of Rest during embryonic neurogenesis to be examined in vivo. We show that Rest plays a role in suppressing the expression of neuronal genes in cultured neuronal cells in vitro, as well as in non-neuronal cells outside of the central nervous system, but that it is dispensable for embryonic neurogenesis in vivo. Our findings highlight the significance of extrinsic signals for the proper intrinsic regulation of neuronal gene expression levels in the specification of cell fate during embryonic neurogenesis in vivo.