• Media type: E-Article
  • Title: c-Jun is a negative regulator of myelination
  • Contributor: 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.
  • imprint: Rockefeller University Press, 2008
  • Published in: The Journal of Cell Biology
  • Language: English
  • DOI: 10.1083/jcb.200803013
  • ISSN: 1540-8140; 0021-9525
  • Origination:
  • Footnote:
  • Description: <jats:p>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.</jats:p>
  • Access State: Open Access