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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Axons / metabolism*
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Axons / ultrastructure
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Cell Differentiation / genetics*
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Cells, Cultured
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Coculture Techniques
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Fetus
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Ganglia, Spinal / cytology
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Ganglia, Spinal / embryology
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Ganglia, Spinal / metabolism
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Gene Expression Regulation, Developmental / genetics*
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Mice
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Mutation / genetics
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Myelin Sheath / metabolism*
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Myelin Sheath / ultrastructure
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Neurons, Afferent / cytology
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Neurons, Afferent / metabolism
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Peripheral Nervous System / embryology*
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Peripheral Nervous System / metabolism*
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Peripheral Nervous System / ultrastructure
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Rats
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Schwann Cells / metabolism*
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Schwann Cells / ultrastructure
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Sciatic Nerve / cytology
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Sciatic Nerve / growth & development
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Sciatic Nerve / metabolism
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Transcription Factor RelA
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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NF-kappa B
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Protein Subunits
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Transcription Factor RelA
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Transcription Factors