The AP-1 Transcription Factor c-Jun Is Required for Efficient Axonal Regeneration

• Published in: Neuron (Cambridge, Mass.) Vol. 43; no. 1; pp. 57 - 67
• Main Authors: Raivich, Gennadij, Bohatschek, Marion, Da Costa, Clive, Iwata, Osuke, Galiano, Matthias, Hristova, Maria, Nateri, Abdolrahman S, Makwana, Milan, Riera-Sans, Lluı́s, Wolfer, David P, Lipp, Hans-Peter, Aguzzi, Adriano, Wagner, Erwin F, Behrens, Axel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.07.2004; Elsevier Limited
• Subjects: Animals; Apoptosis; Atrophy - genetics; Atrophy - metabolism; Axotomy; Brain research; Cell Death - genetics; Down-Regulation - genetics; Facial Nerve - cytology; Facial Nerve - growth & development; Facial Nerve - metabolism; Facial Nerve Injuries - genetics; Facial Nerve Injuries - metabolism; Galanin - metabolism; Gliosis - genetics; Growth Cones - metabolism; Growth Cones - ultrastructure; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Integrins - metabolism; Kinases; Lymphocyte Activation - genetics; Mice; Mice, Transgenic; Microglia - cytology; Microglia - metabolism; Motor Neurons - cytology; Motor Neurons - metabolism; Muscle, Skeletal - innervation; Nerve Regeneration - genetics; Neurogenesis; Neuronal Plasticity - genetics; Phosphorylation; Proteins; Proto-Oncogene Proteins c-jun - deficiency; Proto-Oncogene Proteins c-jun - genetics; Recovery of Function - genetics; Rodents; Transcription Factor AP-1 - metabolism; Transcription factors
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2004.06.005

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.