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Sox21 promotes the progression of vertebrate neurogenesis

Nature Neuroscience volume 8, pages 995–1001 (2005)Cite this article

Abstract

The generation of neurons constitutes the foundation of nervous system development, yet the mechanisms underlying neurogenesis are not well established. The HMG-box transcription factors Sox1, Sox2 and Sox3 (Sox1–3) have previously been shown to suppress neurogenesis by maintaining neural cells in an undifferentiated state. Here we report that another HMG-box protein, Sox21, has the opposite activity and promotes neuronal differentiation. Using genetic studies in the chick embryo, we found that Sox21 mediates this function by counteracting the activity of Sox1–3. Accordingly, the balance of Sox21 and Sox1–3 activities determines whether neural cells remain as progenitors or commit to differentiation. Proneural basic helix-loop-helix proteins are essential for the establishment of neuronal fates. We now show that proneural proteins promote neurogenesis by upregulating Sox21 expression. These data establish a key role for Sox21 in the progression of neuronal differentiation and indicate that an important role of proneural proteins is their capacity to upregulate the expression of Sox21.

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Figure 1: Expression of Sox21 in the developing CNS.
Figure 2: Sox21 functions as a transcriptional repressor.
Figure 3: The activities of Sox21 and Sox3 are distinguished by their C-terminal regions.
Figure 4: Sox21 counterbalances the activity of Sox1–3.
Figure 5: Decreased levels of Sox21 protein inhibit neurogenesis.
Figure 6: Sox21 expression is upregulated by proneural protein activity.

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Acknowledgements

We thank H. Kondoh for Sox21 chick cDNA, and we are grateful to J. Ericson, T. Perlmann and members of the Muhr lab for discussions and comments on the manuscript. J.M. is supported by The Swedish Natural Research Council, The Swedish Foundation for Strategic Research, the Ake Wiberg Research Foundation, the Magnus Bergvall Foundation, the Jeansson Research Foundations and the Ludwig Institute for Cancer Research.

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  1. Ludwig Institute for Cancer Research, Karolinska Institute, Box 240, SE-171 77, Stockholm, Sweden

    Magnus Sandberg, Magdalena Källström & Jonas Muhr

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  1. Magnus Sandberg
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Correspondence to Jonas Muhr.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Id2 represses the generation of neurons but not Sox21 activity. (PDF 1070 kb)

Supplementary Fig. 2

Synergistic activity of Sox21 and Ngn2 during neurogenesis. (PDF 2333 kb)

Supplementary Fig. 3

Proposed model of a transcriptional pathway regulating neurogenesis. (PDF 814 kb)

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Sandberg, M., Källström, M. & Muhr, J. Sox21 promotes the progression of vertebrate neurogenesis. Nat Neurosci 8, 995–1001 (2005). https://doi.org/10.1038/nn1493

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