Vertebrate neurogenesis is counteracted by Sox1-3 activity

Vertebrate neurogenesis is counteracted by Sox1-3 activity
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DOI:
10.1038/nn1131
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发表时间:
2003-11-01
影响因子:
25
通讯作者:
Muhr, J
Muhr, J
中科院分区:
医学1区
文献类型:
--
作者:
Bylund, M;Andersson, E;Muhr, J

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干细胞生成神经元涉及原神经碱性螺旋-环-螺旋(bHLH)蛋白的活性,但这些蛋白使干细胞不可逆地向神经元分化的机制尚不清楚。在这里,我们报告转录因子 Sox1、Sox2 和 Sox3 (Sox1-3) 的表达是神经发生的关键决定因素。使用鸡卵内电穿孔,我们发现 Sox1-3 转录因子通过抵消原神经蛋白的活性来保持神经细胞不分化。相反,原神经 bHLH 蛋白指导神经元分化的能力关键取决于它们抑制 CNS 祖细胞中 Sox1-3 表达的能力。这些数据表明,干细胞产生神经元取决于原神经蛋白对 Sox1-3 表达的抑制。
The generation of neurons from stem cells involves the activity of proneural basic helix-loop-helix (bHLH) proteins, but the mechanism by which these proteins irreversibly commit stem cells to neuronal differentiation is not known. Here we report that expression of the transcription factors Sox1, Sox2 and Sox3 (Sox1-3) is a critical determinant of neurogenesis. Using chick in ovo electroporation, we found that Sox1-3 transcription factors keep neural cells undifferentiated by counteracting the activity of proneural proteins. Conversely, the capacity of proneural bHLH proteins to direct neuronal differentiation critically depends on their ability to suppress Sox1-3 expression in CNS progenitors. These data suggest that the generation of neurons from stem cells depends on the inhibition of Sox1-3 expression by proneural proteins.