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

Nickols JC, Valentine W, Kanwal S, Carter BD
Nat Neurosci. 2003 6 (2): 161-7

PMID: 12514737 · DOI:10.1038/nn995

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.

MeSH Terms (20)

Animals Axons Cell Differentiation Cells, Cultured Coculture Techniques Fetus Ganglia, Spinal Gene Expression Regulation, Developmental Mice Mutation Myelin Sheath Neurons, Afferent NF-kappa B Peripheral Nervous System Protein Subunits Rats Schwann Cells Sciatic Nerve Transcription Factor RelA Transcription Factors

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