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Nat Neurosci. 2003 Feb;6(2):161-7.

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

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

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.

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PMID:
12514737
DOI:
10.1038/nn995
[Indexed for MEDLINE]

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