Neuronal c-Jun is required for successful axonal regeneration, but the effects of phosphorylation of its N-terminus are moderate.
Bottom Line: Although neural c-Jun is essential for successful peripheral nerve regeneration, the cellular basis of this effect and the impact of c-Jun activation are incompletely understood.The effects of substituting serine 63 and 73 phosphoacceptor sites (junAA), or of global deletion of individual kinases responsible for N-terminal c-Jun phosphorylation were mild. junAA mutants showed decrease in neuronal cell size, a moderate reduction in post-axotomy CD44 levels and slightly increased astrogliosis.Deletion of JNK2 had no effect.
Affiliation: Perinatal Brain Repair Group, Inst Women's Health, University College London, London, UK.Show MeSH
Related in: MedlinePlus
Mentions: Cell type specific c-jun gene deletion was achieved by crossing mice with a floxed c-jun allele (junF/F) with animals expressing cre recombinase under the control of the synapsin promoter (syn::cre), which targets the junΔS recombination specifically to neurons (Kügler et al.2001; Zhu et al.2001). Homozygous JunAA and wild-type (wt) mice were derived as offspring of heterozygous (AA/wt) breeder pairs. JNK1, 2 and 3 knockout mice and their controls were produced from F2 homozygous breeder pairs derived from heterozygous mice on C57Bl/6 background. All mutants used in the current study displayed normal brain structure and histology on H&E and NeuN stains on forebrain (cortex, hippocampus, basal ganglia) and hind-brain (cerebellum, metencephalon) sections (not shown). Homozygous junΔS recombination was associated with disappearance of basal immunoreactivity throughout the brain, for example in hippocampus and dentate gyrus (Fig. 1a and b), or the uninjured facial motor nucleus (Fig. 1c and d). Motoneuron c-Jun immunoreactivity is strongly up-regulated by facial nerve cut (Fig. 1f) and this increase was abolished in the junΔS mutant (Fig. 1e). Previous study from our groups revealed the disappearance of phospho-serine63 immunoreactivity in the neuronal nuclei of the axotomized facial motor nucleus in junAA mice but also a persistence of phosphoserine 73-like and as well as of total c-Jun immunoreactivity. In the same study, single JNK deletions were not associated with changes in overall phospho-Jun immunoreactivity (Brecht et al.2005). This persistence of total c-Jun immunoreactivity in neuronal nuclei of the axotomized facial motor nucleus in the junAA mice was also reconfirmed in the current study (data not shown).
Affiliation: Perinatal Brain Repair Group, Inst Women's Health, University College London, London, UK.