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c-Jun is a negative regulator of myelination
Correspondence to Kristján R. Jessen: k.jessen{at}ucl.ac.uk
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.
D.B. Parkinson's present address is Peninsula Medical School, Tamar Science Park, Plymouth, Devon PL6 8BU, UK.
Abbreviations used in this paper: db-cAMP, dibutyryl cAMP; DM, defined medium; DRG, dorsal root ganglion; E, embryonic day; MBP, myelin basic protein; MKK7, MAPK kinase 7; NRG-1, β–neuregulin-1; P, postnatal day; P0, protein zero.
© 2008 Parkinson et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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