Bylund Magdalena, Andersson Elisabeth, Novitch Bennett G, Muhr Jonas
Ludwig Institute of Cancer Research, Karolinska Institute, Box 240, SE-171 77 Stockholm, Sweden.
Nat Neurosci. 2003 Nov;6(11):1162-8. doi: 10.1038/nn1131. Epub 2003 Sep 28.
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.
从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定向于神经元分化的机制尚不清楚。在此我们报告,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。利用鸡胚在体电穿孔技术,我们发现Sox1-3转录因子通过对抗原神经蛋白的活性使神经细胞保持未分化状态。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在中枢神经系统祖细胞中抑制Sox1-3表达的能力。这些数据表明,从干细胞生成神经元依赖于原神经蛋白对Sox1-3表达的抑制。