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c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration.

Arthur-Farraj, PJ; Latouche, M; Wilton, DK; Quintes, S; Chabrol, E; Banerjee, A; Woodhoo, A; ... Jessen, KR; + view all (2012) c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron , 75 (4) 633 - 647. 10.1016/j.neuron.2012.06.021. Green open access

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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.

Type: Article
Title: c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration.
Location: US
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuron.2012.06.021
Publisher version: http://dx.doi.org/10.1016/j.neuron.2012.06.021
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3657176
Keywords: Adenoviridae, Analysis of Variance, Animals, Benzofurans, Cell Movement, Disease Models, Animal, Gene Expression Regulation, Genetic Vectors, Macrophages, Mice, Mice, Transgenic, Microfluidic Analytical Techniques, Microscopy, Electron, Transmission, Motor Neurons, Myelin Sheath, Nerve Regeneration, Proto-Oncogene Proteins c-jun, Schwann Cells, Sciatic Neuropathy, Spinal Cord
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health > Maternal and Fetal Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/1364750
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