title: c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration.
abstract: The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Arthur-Farraj
authors.forename: Morwena
authors.initials: M
authors.lastname: Latouche
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Wilton
authors.forename: Susanne
authors.initials: S
authors.lastname: Quintes
authors.forename: Elodie
authors.initials: E
authors.lastname: Chabrol
authors.forename: Ambily
authors.initials: A
authors.lastname: Banerjee
authors.forename: Ashwin
authors.initials: A
authors.lastname: Woodhoo
authors.forename: Billy
authors.initials: B
authors.lastname: Jenkins
authors.forename: Mary
authors.initials: M
authors.lastname: Rahman
authors.forename: Mark
authors.initials: M
authors.lastname: Turmaine
authors.forename: Grzegorz K
authors.initials: GK
authors.lastname: Wicher
authors.forename: Richard
authors.initials: R
authors.lastname: Mitter
authors.forename: Linda
authors.initials: L
authors.lastname: Greensmith
authors.forename: Axel
authors.initials: A
authors.lastname: Behrens
authors.forename: Gennadij
authors.initials: G
authors.lastname: Raivich
authors.forename: Rhona
authors.initials: R
authors.lastname: Mirsky
authors.forename: Kristján R
authors.initials: KR
authors.lastname: Jessen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001572:Benzofurans; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D005822:Genetic Vectors / Q000502:physiology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D046210:Microfluidic Analytical Techniques; D046529:Microscopy, Electron, Transmission; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D013116:Spinal Cord / Q000473:pathology
chemical_list: D001572:Benzofurans; D016755:Proto-Oncogene Proteins c-jun; C038675:true blue