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.
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