KEGG   PATHWAY: map04361
Entry
map04361                    Pathway                                
Name
Axon regeneration
Description
Many mature central nervous system (CNS) neurons in non-mammals, such as C. elegans, Drosophila, and zebrafish, are able to regenerate after injuries. The MAPK cascade, DLK-1/MKK-4/PMK-3/MAK2, is identified as an essential signaling pathway involved in axon regeneration in C. elegans. Calcium influx, which is triggered by axotomy, is implicated in DLK-1 activation. Another MAP kinase pathway, MLK-1/MEK-1/KGB-1, acts in parallel with the DLK-1 pathway to control growth-cone formation after axotomy. SVH-1, a homolog of the mammalian hepatocyte growth factor and its receptor SVH-2 function upstream of the MLK-1 pathway to promote axon regeneration. There are also inhibitors of regeneration, such as lin-12/Notch and efa-6. It is possible that the C. elegans pathways that inhibit regeneration function to stabilize the mature, uninjured nervous system.
Class
Organismal Systems; Development and regeneration
Pathway map
map04361  Axon regeneration
map04361

Reference
  Authors
Hisamoto N, Matsumoto K
  Title
Signal transduction cascades in axon regeneration: insights from C. elegans.
  Journal
Curr Opin Genet Dev 44:54-60 (2017)
DOI:10.1016/j.gde.2017.01.010
Reference
  Authors
Chen L, Chisholm AD
  Title
Axon regeneration mechanisms: insights from C. elegans.
  Journal
Trends Cell Biol 21:577-84 (2011)
DOI:10.1016/j.tcb.2011.08.003
Reference
  Authors
Saijilafu, Zhang BY, Zhou FQ
  Title
Signaling pathways that regulate axon regeneration.
  Journal
Neurosci Bull 29:411-20 (2013)
DOI:10.1007/s12264-013-1357-4
Reference
  Authors
El Bejjani R, Hammarlund M
  Title
Neural regeneration in Caenorhabditis elegans.
  Journal
Annu Rev Genet 46:499-513 (2012)
DOI:10.1146/annurev-genet-110711-155550
Reference
  Authors
Chisholm AD
  Title
Cytoskeletal dynamics in Caenorhabditis elegans axon regeneration.
  Journal
Annu Rev Cell Dev Biol 29:271-97 (2013)
DOI:10.1146/annurev-cellbio-101512-122311
Reference
  Authors
Hammarlund M, Jin Y
  Title
Axon regeneration in C. elegans.
  Journal
Curr Opin Neurobiol 27:199-207 (2014)
DOI:10.1016/j.conb.2014.04.001
Reference
  Authors
Pastuhov SI, Hisamoto N, Matsumoto K
  Title
MAP kinase cascades regulating axon regeneration in C. elegans.
  Journal
Proc Jpn Acad Ser B Phys Biol Sci 91:63-75 (2015)
DOI:10.2183/pjab.91.63
Reference
  Authors
Li C, Hisamoto N, Matsumoto K
  Title
Axon Regeneration Is Regulated by Ets-C/EBP Transcription Complexes Generated by Activation of the cAMP/Ca2+ Signaling Pathways.
  Journal
PLoS Genet 11:e1005603 (2015)
DOI:10.1371/journal.pgen.1005603
Reference
  Authors
Chen L, Chuang M, Koorman T, Boxem M, Jin Y, Chisholm AD
  Title
Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase.
  Journal
Elife 4:e08695 (2015)
DOI:10.7554/eLife.08695
Reference
  Authors
Pastuhov SI, Fujiki K, Nix P, Kanao S, Bastiani M, Matsumoto K, Hisamoto N
  Title
Endocannabinoid-Goalpha signalling inhibits axon regeneration in Caenorhabditis elegans by antagonizing Gqalpha-PKC-JNK signalling.
  Journal
Nat Commun 3:1136 (2012)
DOI:10.1038/ncomms2136
Reference
  Authors
Belin S, Norsworthy M, He Z
  Title
Independent control of aging and axon regeneration.
  Journal
Cell Metab 19:354-6 (2014)
DOI:10.1016/j.cmet.2014.02.014
Reference
  Authors
Byrne AB, Walradt T, Gardner KE, Hubbert A, Reinke V, Hammarlund M
  Title
Insulin/IGF1 signaling inhibits age-dependent axon regeneration.
  Journal
Neuron 81:561-73 (2014)
DOI:10.1016/j.neuron.2013.11.019
Reference
  Authors
Po MD, Calarco JA, Zhen M
  Title
Releasing the inner inhibition for axon regeneration.
  Journal
Neuron 73:207-9 (2012)
DOI:10.1016/j.neuron.2012.01.002
Reference
  Authors
El Bejjani R, Hammarlund M
  Title
Notch signaling inhibits axon regeneration.
  Journal
Neuron 73:268-78 (2012)
DOI:10.1016/j.neuron.2011.11.017
Reference
  Authors
Gabel CV, Antoine F, Chuang CF, Samuel AD, Chang C
  Title
Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in C. elegans.
  Journal
Development 135:1129-36 (2008)
DOI:10.1242/dev.013995
Reference
  Authors
Hubert T, Wu Z, Chisholm AD, Jin Y
  Title
S6 kinase inhibits intrinsic axon regeneration capacity via AMP kinase in Caenorhabditis elegans.
  Journal
J Neurosci 34:758-63 (2014)
DOI:10.1523/JNEUROSCI.2886-13.2014
Reference
  Authors
Zou Y, Chiu H, Zinovyeva A, Ambros V, Chuang CF, Chang C
  Title
Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers.
  Journal
Science 340:372-376 (2013)
DOI:10.1126/science.1231321
Reference
  Authors
Nix P, Bastiani M
  Title
Neuroscience. Heterochronic genes turn back the clock in old neurons.
  Journal
Science 340:282-3 (2013)
DOI:10.1126/science.1237921
Related
pathway
map04150  mTOR signaling pathway
map04910  Insulin signaling pathway
KO pathway
ko04361   
LinkDB

DBGET integrated database retrieval system