Activation of the transcription factor NF-kappaB in Schwann cells is required for peripheral myelin formation.
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.
Nickols
Joshua C
JC
Vanderbilt University Medical School, Vanderbilt University, Nashville, Tennessee 37232, USA.
Valentine
William
W
Kanwal
Sujata
S
Carter
Bruce D
BD
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005333:Fetus; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D017933:Peripheral Nervous System / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D016328:NF-kappa B; D021122:Protein Subunits; D051996:Transcription Factor RelA; D014157:Transcription Factors