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

Nat Neurosci. 2003 Feb;6(2):161-7. doi: 10.1038/nn995.

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-kappaB. In rat sciatic nerves, NF-kappaB 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-kappaB activation paralleled myelination, and blocking its activity or using cells from mice lacking the NF-kappaB subunit p65 markedly attenuated myelination. Inhibiting NF-kappaB 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-kappaB is an essential signal for the progression of axon-associated Schwann cells into a myelinating phenotype.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axons / ultrastructure
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Coculture Techniques
  • Fetus
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / embryology
  • Ganglia, Spinal / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Mice
  • Mutation / genetics
  • Myelin Sheath / metabolism*
  • Myelin Sheath / ultrastructure
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Neurons, Afferent / cytology
  • Neurons, Afferent / metabolism
  • Peripheral Nervous System / embryology*
  • Peripheral Nervous System / metabolism*
  • Peripheral Nervous System / ultrastructure
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Rats
  • Schwann Cells / metabolism*
  • Schwann Cells / ultrastructure
  • Sciatic Nerve / cytology
  • Sciatic Nerve / growth & development
  • Sciatic Nerve / metabolism
  • Transcription Factor RelA
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • NF-kappa B
  • Protein Subunits
  • Transcription Factor RelA
  • Transcription Factors