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PMID:15233917
Citation |
Raivich, G, Bohatschek, M, Da Costa, C, Iwata, O, Galiano, M, Hristova, M, Nateri, AS, Makwana, M, Riera-Sans, L, Wolfer, DP, Lipp, HP, Aguzzi, A, Wagner, EF and Behrens, A (2004) The AP-1 transcription factor c-Jun is required for efficient axonal regeneration. Neuron 43:57-67 |
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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 alpha7beta1 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. |
Links |
PubMed Online version:10.1016/j.neuron.2004.06.005 |
Keywords |
Animals; Antigens, CD44/genetics; Antigens, CD44/metabolism; Atrophy/genetics; Atrophy/metabolism; Axotomy; 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; Integrins/metabolism; Lymphocyte Activation/genetics; Mice; Mice, Transgenic; Microglia/cytology; Microglia/metabolism; Motor Neurons/cytology; Motor Neurons/metabolism; Muscle, Skeletal/innervation; Nerve Regeneration/genetics; Neuronal Plasticity/genetics; Proto-Oncogene Proteins c-jun/deficiency; Proto-Oncogene Proteins c-jun/genetics; Recovery of Function/genetics; Transcription Factor AP-1/metabolism |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
MOUSE:JUN |
involved_in |
GO:0043524: negative regulation of neuron apoptotic process |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2445420 |
P |
Seeded From UniProt |
complete | |
MOUSE:JUN |
involved_in |
GO:0031103: axon regeneration |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2445420 |
P |
Seeded From UniProt |
complete | |
MOUSE:JUN |
involved_in |
GO:0001774: microglial cell activation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2445420 |
P |
Seeded From UniProt |
complete | |
See also
References
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