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Activation of the transcription factor NF-κB in Schwann cells is required for peripheral myelin formation

Nature Neuroscience volume 6, pages 161–167 (2003)Cite this article

Abstract

Peripheral myelin formation is initiated by axonal cues that trigger a differentiation program in associated Schwann cells. Here, we define one essential differentiation signal: activation of the transcription factor NF-κB. In rat sciatic nerves, NF-κB was highly upregulated in pre-myelinating Schwann cells, and then its expression progressively declined until it was nearly absent in adults. Similarly, in co-cultures of Schwann cells and sensory neurons, NF-κB activation paralleled myelination, and blocking its activity or using cells from mice lacking the NF-κB subunit p65 markedly attenuated myelination. Inhibiting NF-κB also prevented activation of Oct-6, a transcription factor induced by axonal contact and required for proper myelin formation. These results show that the activation of NF-κB is an essential signal for the progression of axon-associated Schwann cells into a myelinating phenotype.

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Figure 1: NF-κB is activated in the perinatal rat sciatic nerve.
Figure 2: NF-κB is activated in Schwann cells during myelination in vitro.
Figure 3: Inhibition of NF-κB activation prevents myelination.
Figure 4: p65 null cultures show a myelin deficiency.
Figure 5: IκBm-treated Schwann cells fail to ensheath axons.
Figure 6: Proliferation of IκBm- or GFP-adenovirus infected Schwann cells is similar.
Figure 7: Normal basal lamina formation by NF-κB inhibitor–treated cultures.
Figure 8: NF-κB activation is required for Oct-6 induction.

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Acknowledgements

The authors thank J.L. Salzer, S.O. Yoon and members of the Carter lab for helpful suggestions and the Vanderbilt Cell Imaging Core for technical support. We also are grateful to Regeneron Corp. for providing the neurotrophins. This work was supported by a NIH grant (NS38220), a Christopher Reeve Paralysis Foundation grant (CAC1-9803-2) and a Wadsworth Foundation grant to B.D.C., a NIH training grant (MH19732) to J.C.N. and a NIH grant (ES06387) to W.V.

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Authors and Affiliations

  1. Vanderbilt University Medical School, Vanderbilt University, Nashville, 37232, Tennessee, USA

    Joshua C. Nickols, William Valentine, Sujata Kanwal & Bruce D. Carter

  2. Center for Molecular Neuroscience, Vanderbilt University, Nashville, 37232, Tennessee, USA

    Joshua C. Nickols, William Valentine & Bruce D. Carter

  3. Department of Pathology, Vanderbilt University, Nashville, 37232, Tennessee, USA

    William Valentine

  4. Department of Biochemistry, Vanderbilt University, Nashville, 37232, Tennessee, USA

    Sujata Kanwal & Bruce D. Carter

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Correspondence to Bruce D. Carter.

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Nickols, J., Valentine, W., Kanwal, S. et al. Activation of the transcription factor NF-κB in Schwann cells is required for peripheral myelin formation. Nat Neurosci 6, 161–167 (2003). https://doi.org/10.1038/nn995

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