Neural bHLH genes control the neuronal versus glial fate decision in cortical progenitors

Neural bHLH genes control the neuronal versus glial fate decision in cortical progenitors
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DOI:
10.1016/s0896-6273(01)00214-8
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发表时间:
2001-02-01
期刊:
影响因子:
16.2
通讯作者:
Guillemot, F
Guillemot, F
中科院分区:
医学1区
文献类型:
--
作者:
Nieto, M;Schuurmans, C;Guillemot, F

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我们已经解决了前神经bHLH基因Neurogenin 2(Ngn 2)和Mash 1在神经干细胞选择神经元和神经胶质细胞命运中的作用。我们发现,这两种基因突变的小鼠在大脑皮层发育中存在严重缺陷,包括神经发生减少和过早和过度生成星形胶质细胞前体。对培养中的野生型和突变型皮质祖细胞的分析表明,大部分Ngn 2; Mash 1双突变型祖细胞未能采用神经元命运,而是保持多能性或进入星形胶质细胞分化途径。总之,这些结果表明,原神经基因参与皮质祖细胞的谱系限制,促进神经元命运的获得和抑制星形胶质细胞命运。
We have addressed the role of the proneural bHLH genes Neurogenin2 (Ngn2) and Mash1 in the selection of neuronal and glial fates by neural stem cells. We show that mice mutant for both genes present severe defects in development of the cerebral cortex, including a reduction of neurogenesis and a premature and excessive generation of astrocytic precursors. An analysis of wild-type and mutant cortical progenitors in culture showed that a large fraction of Ngn2; Mash1 double-mutant progenitors failed to adopt a neuronal fate, instead remaining pluripotent or entering an astrocytic differentiation pathway. Together, these results demonstrate that proneural genes are involved in lineage restriction of cortical progenitors, promoting the acquisition of the neuronal fate and inhibiting the astrocytic fate.