Parkinson, DB and Bhaskaran, A and Arthur-Farraj, P and Noon, LA and Woodhoo, A and Lloyd, AC and Feltri, ML and Wrabetz, L and Behrens, A and Mirsky, R and Jessen, KR (2008) c-Jun is a negative regulator of myelination. J CELL BIOL , 181 (4) 625 - 637. 10.1083/jcb.200803013.
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.
|Title:||c-Jun is a negative regulator of myelination|
|Open access status:||An open access publication|
|Publisher version:||http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC2386103/?tool=pubmed|
|Keywords:||SCHWANN-CELL MYELINATION, PERIPHERAL NERVOUS-SYSTEM, WALLERIAN DEGENERATION, MACROPHAGE RECRUITMENT, GENE-EXPRESSION, GLIAL-CELLS, IN-VITRO, NERVES, PROLIFERATION, DIFFERENTIATION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Cell and Developmental Biology|
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Laboratory for Molecular Cell Biology
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