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

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.

Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat

“…These key networks cover the most important pathways that play important roles in regulating this differential gene expression through mainly biological GO processes during WD after sciatic nerve injury. The data shown here are consistent with published reports [15][16][17] and supported the conclusion that developing and regenerating peripheral nerves exhibit differences in genetic programs. Further, the data revealed that signal transducers were significantly regulated in the lesioned distal stump after sciatic nerve injury.…”

“…Further, the data revealed that signal transducers were significantly regulated in the lesioned distal stump after sciatic nerve injury. The molecules that were significantly up-or down-regulated after such injury are known to modulate the signal pathways in key networks [15,[29][30][31][32] . It is supposed that the key networks play roles in Schwann cell activation and proliferation as well as WD and subsequent regeneration [33][34][35] .…”

“…Many genes and related proteins are differentially expressed during WD, the latter including cytokines, neurotrophic factors, axonal myelin and cell adhesion molecules [11][12][13][14][15][16][17][18] . The development of tissue biochemistry and molecular biology, together with improvements in microscopic resolution, has largely facilitated the understanding of the significance of WD in the processes of nerve degeneration and subsequent repair/regeneration [11][12][13][14][15][16][17][18] . Understanding the molecular mechanisms of axonal debris and myelin clearance after processed using GeneSpring GCOS1.2 software.…”

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

“…Moreover, hippocampal granule cell proliferation is increased by activation of cAMP signaling and reduced by CREB inhibition [148], and combined disruption of CREB and CREM leads to neurodegeneration in the hippocampus and in the dorsolateral striatum [121]. In contrast, conditional knockout of c-Jun using the Nestin gene 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 promoter does not affect hippocampal-dependent behavior or brain morphology [149], but greatly impairs axonal regeneration, supporting a role for this AP-1 family member in neuronal maturation. ATF2 is also found in the human hippocampus and its expression is reduced in patients with Parkinson´s and Alzheimer´s disease [89].…”

Intracellular control of developmental and regenerative axon growth

“…In conditionally c-Jun null mice, axon regeneration of facial nerve was significantly delayed (Raivich et al 2004). In contrast, lack of c-Jun in neurons had little effect on axon growth during development, suggesting that c-Jun specifically regulates regenerative axon growth (Raivich et al 2004).…”