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

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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.