The AP-1 transcription factor c-Jun is required for efficient axonal regeneration.
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.
Raivich
Gennadij
G
Perinatal Brain Repair Group, Department of Obstetrics and Gynaecology, University College London, 86-96 Chenies Mews, London WC1E 6HX, United Kingdom.
Bohatschek
Marion
M
Da Costa
Clive
C
Iwata
Osuke
O
Galiano
Matthias
M
Hristova
Maria
M
Nateri
Abdolrahman S
AS
Makwana
Milan
M
Riera-Sans
Lluís
L
Wolfer
David P
DP
Lipp
Hans-Peter
HP
Aguzzi
Adriano
A
Wagner
Erwin F
EF
Behrens
Axel
A
D000818:Animals; D001284:Atrophy / Q000235:genetics / Q000378:metabolism; D019771:Axotomy; D016923:Cell Death / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005154:Facial Nerve / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D020220:Facial Nerve Injuries / Q000235:genetics / Q000378:metabolism*; D019004:Galanin / Q000378:metabolism; D005911:Gliosis / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000294:innervation; D009416:Nerve Regeneration / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000172:deficiency / Q000235:genetics*; D020127:Recovery of Function / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D018960:Hyaluronan Receptors; D016023:Integrins; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D019004:Galanin; C082908:integrin alpha7beta1