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Vertebrate neurogenesis is counteracted by Sox1–3 activity

Abstract

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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Figure 1: Expression of Sox1–3 in the developing CNS.
Figure 2: Sox1–3 activity prevents neuronal differentiation.
Figure 3: Sox1–3 are transcriptional activators.
Figure 4: Repression of Sox1–3 target genes promotes differentiation.
Figure 5: Ngn2 activity represses Sox1–3 expression.
Figure 6: Sox3 counteracts Ngn2 activity.

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Acknowledgements

We thank M. Uchikawa for Sox1–3 chick cDNA and T. Reh for Cash1 cDNA. We are grateful to P. Bailey, T. Edlund, J. Ericson, U. Lendahl, T. Perlmann and S. Wilson for discussions and comments on the manuscript. J.M. is supported by the Swedish Natural Research Council, the Swedish Foundation for Strategic Research and the Ludwig Institute of Cancer Research.

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Correspondence to Jonas Muhr.

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Supplementary information

Supplementary Fig. 1.

Regulation of c-Hairy1 and c-Hes5 expression by Ngn2 and Sox3. (a-c) Misexpression of Ngn2 (a) increased the expression of c-Hairy1 (b) in a fraction of the transfected cell, whereas c-Hes5 expression was markedly upregulated throughout the Ngn2 electroporated side (c). Embryos were analyzed 10 h after electroporation. (d-f) The expression of c-Hairy1 was similar in the Sox3 electroporated side compared to the control side (d and e), whereas the expression level of c-Hes5 was slightly decreased in Sox3 transfected cells (f). Embryos were analyzed 44 h after electroporation. (JPG 54 kb)

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Bylund, M., Andersson, E., Novitch, B. et al. Vertebrate neurogenesis is counteracted by Sox1–3 activity. Nat Neurosci 6, 1162–1168 (2003). https://doi.org/10.1038/nn1131

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