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- Title
c-Jun is a negative regulator of myelination.
- Authors
Parkinson, David B; Bhaskaran, Ambily; Arthur-Farraj, Peter; Noon, Luke A; Woodhoo, Ashwin; Lloyd, Alison C; Feltri, M Laura; Wrabetz, Lawrence; Behrens, Axel; Mirsky, Rhona; Jessen, Kristján R
- 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.
- Publication
The Journal of cell biology, 2008, Vol 181, Issue 4, p625
- ISSN
1540-8140
- Publication type
Journal Article
- DOI
10.1083/jcb.200803013