The AP-1 transcription factor c-Jun is required for efficient axonal regeneration

Raivich, Gennadij; Bohatschek, Marion; Da Costa, Clive; Iwata, Osuke; Galiano, Matthias; Hristova, Maria; Nateri, Abdolrahman S.; Makwana, Milan; Riera-Sans, Lluís; Wolfer, David P.; Lipp, Hans Peter; Aguzzi, Adriano; Wagner, Erwin F.; Behrens, Axel

Abstract

Nerve injury triggers numerous changes in the injured neurons and surrounding nonneuronal cells that ultimately result in successful target reinnervation or cell death. c-Jun is a component of the heterodimeric AP-1 transcription factor, and c-Jun is highly expressed in response to neuronal trauma. Here we have investigated the role of c-jun during axonal regeneration using mice lacking c-jun in the central nervous system. After transection of the facial nerve, the absence of c-Jun caused severe defects in several aspects of the axonal response, including perineuronal sprouting, lymphocyte recruitment, and microglial activation. c-Jun-deficient motorneurons were atrophic, resistant to axotomy-induced cell death, and showed reduced target muscle reinnervation. Expression of CD44, galanin, and α7β1 integrin, molecules known to be involved in regeneration, was greatly impaired, suggesting a mechanism for c-Jun-mediated axonal growth. Taken together, our results identify c-Jun as an important regulator of axonal regeneration in the injured central nervous system.

Citation

Raivich, G., Bohatschek, M., Da Costa, C., Iwata, O., Galiano, M., Hristova, M., Nateri, A. S., Makwana, M., Riera-Sans, L., Wolfer, D. P., Lipp, H. P., Aguzzi, A., Wagner, E. F., & Behrens, A. (2004). The AP-1 transcription factor c-Jun is required for efficient axonal regeneration. Neuron, 43(1), 57-67. https://doi.org/10.1016/j.neuron.2004.06.005

• Journal Article Type: Article
• Acceptance Date: Jun 4, 2024
• Online Publication Date: Jul 7, 2004
• Publication Date: Jul 8, 2004
• Deposit Date: Sep 11, 2024
• Journal: Neuron
• Print ISSN: 0896-6273
• Electronic ISSN: 1097-4199
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 43
• Issue: 1
• Pages: 57-67
• DOI: https://doi.org/10.1016/j.neuron.2004.06.005
• Public URL: https://nottingham-repository.worktribe.com/output/39458151
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0896627304003575?via%3Dihub