ORCID

Abstract

Schwann cell myelination depends on Krox-20/Egr2 and other promyelin transcription factors that are activated by axonal signals and control the generation of myelin-forming cells. Myelin-forming cells remain remarkably plastic and can revert to the immature phenotype, a process which is seen in injured nerves and demyelinating neuropathies. We report that c-Jun is an important regulator of this plasticity. At physiological levels, c-Jun inhibits myelin gene activation by Krox-20 or cyclic adenosine monophosphate. c-Jun also drives myelinating cells back to the immature state in transected nerves in vivo. Enforced c-Jun expression inhibits myelination in cocultures. Furthermore, c-Jun and Krox-20 show a cross-antagonistic functional relationship. c-Jun therefore negatively regulates the myelinating Schwann cell phenotype, representing a signal that functionally stands in opposition to the promyelin transcription factors. Negative regulation of myelination is likely to have significant implications for three areas of Schwann cell biology: the molecular analysis of plasticity, demyelinating pathologies, and the response of peripheral nerves to injury.

DOI

10.1083/jcb.200803013

Publication Date

2008-05-19

Publication Title

J Cell Biol

Volume

181

Issue

4

First Page

625

Last Page

637

Organisational Unit

Peninsula Medical School

Keywords

Animals, Newborn, Cell Dedifferentiation, Coculture Techniques, Cyclic AMP, DNA-Binding Proteins, Down-Regulation, Early Growth Response Protein 2, Ganglia, Spinal, HMGB Proteins, MAP Kinase Kinase 7, Mice, Myelin Proteins, Myelin Sheath, Octamer Transcription Factor-6, Phosphorylation, Proto-Oncogene Proteins c-jun, Rats, SOXB1 Transcription Factors, Schwann Cells, Transcription Factors, Up-Regulation, Wallerian Degeneration

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