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Genes in Axonal Regeneration

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Abstract

This review explores the molecular and genetic underpinnings of axonal regeneration and functional recovery post-nerve injury, emphasizing its significance in reversing neurological deficits. It presents a systematic exploration of the roles of various genes in axonal regrowth across peripheral and central nerve injuries. Initially, it highlights genes and gene families critical for axonal growth and guidance, delving into their roles in regeneration. It then examines the regenerative microenvironment, focusing on the role of glial cells in neural repair through dedifferentiation, proliferation, and migration. The concept of “traumatic microenvironments” within the central nervous system (CNS) and peripheral nervous system (PNS) is discussed, noting their impact on regenerative capacities and their importance in therapeutic strategy development. Additionally, the review delves into axonal transport mechanisms essential for accurate growth and reinnervation, integrating insights from proteomics, genome-wide screenings, and gene editing advancements. Conclusively, it synthesizes these insights to offer a comprehensive understanding of axonal regeneration’s molecular orchestration, aiming to inform effective nerve injury therapies and contribute to regenerative neuroscience.

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Data Availability

Data are available from the corresponding authors on reasonable request.

Abbreviations

AIS:

Axon initial segment

Ascl1a:

Transcription factor 1a

ASO:

Antisense oligonucleotide

Axl:

AXL receptor tyrosine kinase

BDNF:

Brain-derived neurotrophic factor

BHLH:

Achaete-scute family

Big1:

Brefeldin A–inhibited guanine nucleotide-exchange protein 1

Cacna2d2:

Channel auxiliary subunit alpha2delta 2

cAMP:

Cyclic adenosine monophosphate

Ccl11:

CC chemokine ligand 11

CNS:

Central nervous system

CNTF:

Ciliary-neurotrophic-factor

Creb1:

cAMP-responsive element-binding protein 1

CSPGs:

Chondroitin sulfate proteoglycans

CST:

Corticospinal tract

Ctgfa:

Connective tissue growth factor a

DCC:

Deleted in colorectal carcinoma

Dclk:

Doublecortin-like kinase

Dlg1:

Disks large MAGUK scaffold protein 1

DRG:

Dorsal root ganglion

dSCs:

Dedifferentiated Schwann cells

Efa6:

Arf6 guanine-nucleotide-exchange factor

Egr2:

Early growth response 2

eIF2Bε:

Eukaryotic translation initiation factor 2B epsilon

EMT:

Epithelial-to-mesenchymal transition

Erbb2:

Erb-B2 receptor tyrosine kinase 2

GDNF:

Glial-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

Gjb1:

Gap junction protein beta 1

GSK3b:

Glycogen synthase kinase 3b

Hdac3:

p38 MAP kinase pathways, histone deacetylase 3

Hes5:

hes family BHLH transcription factor 5

HGF:

Hepatocyte growth factor

HIF-1α:

Hypoxia-inducible factor 1α

HMGA2:

High mobility group A2

Hspd1:

Heat shock protein family D member 1

Id2:

Inhibitor of DNA binding 2

Jun:

Transcription factor AP-1

KCC2:

K + -Cl- co-transporter

Kifc1:

Kinesin family member c1

KLF:

Krueppel-like factor

Lif:

Leukemia inhibitory factor

lncRNAs:

Long non-coding RNAs

LPA:

Lysophosphatidic acid

Lrp1:

LDL receptor-related protein 1

Mag:

Myelin-associated glycoprotein

Malat1:

Metastasis-associated lung adenocarcinoma transcript 1

MAPK:

Mitogen-activated protein kinase

Mapt:

Microtubule-associated protein tau

Mbp:

Myelin basic protein

Mcp-1:

Monocyte chemoattractant protein 1

Mertk:

MER proto-oncogene tyrosine kinase

MLKL:

Mixed lineage kinase domain-like protein

Mmp7:

Matrix metalloproteinase 7

MSC:

Mesenchymal-like stem cells

mTOR:

Mammalian target of rapamycin

Myc:

Myc proto-oncogene protein

Ncam:

Neural cell adhesion molecule

NGF:

Nerve growth factor

Ngfr:

Nerve growth factor receptor

NPCs:

Neural precursor cells

P0/Mpz:

Myelin protein zero

Pax3:

Paired box 3

PKA:

Protein kinase A

Pmp22:

Peripheral myelin protein 22

Pten:

Phosphatase and tensin homolog

Rheb1:

ras homolog enriched in brain 1

ROK:

Rho-associated kinase

Slc30a3:

Solute carrier family 30member 3

Slit3:

Slit guidance ligand 3

Socs3:

Suppressor of cytokine signaling 3

Sox 10:

SRY-Box Transcription Factor 10

Srebf1:

Sterol regulatory element binding transcription factor 1

Srf:

Serum response factor

Stat3:

Signal transducer and activator of transcription 3

Tacc/Tac-1:

Transforming acidic coiled coil

Tead4:

tea-domain transcription factor 4

Tet3:

tet methylcytosine dioxygenase 3

TGFβ:

Transforming growth factor-β

TNF-α:

Tumor necrosis factor alpha

TP53:

Tet3 and cellular tumor antigen p53

Trim46:

Tripartite motif containing protein

TRPV2:

Transient receptor potential vanilloid 2

Tsc1:

Tuberous sclerosis complex 1

Tyro3:

TYRO3 protein tyrosine kinase

Unc5B:

unc-5 netrin receptor B

VEGFA:

Vascular endothelial growth factor A

Zeb1:

Zinc-finger E-box-binding 1

References

  1. O’Brien AL, West JM, Saffari TM, Nguyen M, Moore AM (2022) Promoting nerve regeneration: electrical stimulation, gene therapy, and beyond. Physiology (Bethesda) 37(6):0. https://doi.org/10.1152/physiol.00008.2022

  2. Song S, Huang H, Guan X et al (2021) Activation of endothelial Wnt/β-catenin signaling by protective astrocytes repairs BBB damage in ischemic stroke. Prog Neurobiol 199:101963. https://doi.org/10.1016/j.pneurobio.2020.101963

    Article  CAS  PubMed  Google Scholar 

  3. Liu Q, Wang X, Yi S (2018) Pathophysiological changes of physical barriers of peripheral nerves after injury. Front Neurosci 12:597. https://doi.org/10.3389/fnins.2018.00597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wang B, Huang M, Shang D, Yan X, Zhao B, Zhang X (2021) Mitochondrial behavior in axon degeneration and regeneration. Front Aging Neurosci 13:650038. https://doi.org/10.3389/fnagi.2021.650038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Klinman E, Tokito M, Holzbaur ELF (2017) CDK5-dependent activation of dynein in the axon initial segment regulates polarized cargo transport in neurons. Traffic 18(12):808–824. https://doi.org/10.1111/tra.12529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Moore DL, Blackmore MG, Ying H, Kaestner KH, Bixby JL, Lemmon VP, Goldberg JL (2009) KLF family members regulate intrinsic axon regeneration ability. Science 326(5950):298–301. https://doi.org/10.1126/science.1175737

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chen L, Feng P, Zhu X, He S, Duan J, Zhou D (2016) Long non-coding RNA Malat1 promotes neurite outgrowth through activation of ERK/MAPK signalling pathway in N2a cells. J Cell Mol Med 20(11):2102–2110. https://doi.org/10.1111/jcmm.12904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bin Y, Zhou S, Wen H, Qian T, Gao R, Ding G, Ding F, Xiaosong G (2013) Altered long noncoding RNA expressions in dorsal root ganglion after rat sciatic nerve injury. Neurosci Lett 534:117–122. https://doi.org/10.1016/j.neulet.2012.12.014

    Article  CAS  Google Scholar 

  9. Kaselis A, Treinys R, Vosyliūtė R, Šatkauskas S (2014) DRG axon elongation and growth cone collapse rate induced by Sema3A are differently dependent on NGF concentration. Cell Mol Neurobiol 34(2):289–296. https://doi.org/10.1007/s10571-013-0013-x

    Article  CAS  PubMed  Google Scholar 

  10. Alsmadi NZ, Bendale GS, Kanneganti A, Shihabeddin T, Nguyen AH, Hor E, Dash S, Johnston B et al (2018) Glial-derived growth factor and pleiotrophin synergistically promote axonal regeneration in critical nerve injuries. Acta Biomater 78(165):177. https://doi.org/10.1016/j.actbio.2018.07.048

    Article  CAS  Google Scholar 

  11. McWilliams TG, Howard L, Wyatt S, Davies AM (2017) TNF superfamily member APRIL enhances midbrain dopaminergic axon growth and contributes to the nigrostriatal projection in vivo. Exp Neurol 298(Pt A):97–103. https://doi.org/10.1016/j.expneurol.2017.09.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Howard L, McWilliams TG, Wyatt S, Davies AM (2019) CD40 forward signalling is a physiological regulator of early sensory axon growth. Development 146(18):dev176495. https://doi.org/10.1242/dev.176495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li S, Zhang R, Yuan Y, Yi S, Chen Q, Gong L, Liu J, Ding F et al (2017) MiR-340 regulates fibrinolysis and axon regrowth following sciatic nerve injury. Mol Neurobiol 54(6):4379–4389. https://doi.org/10.1007/s12035-016-9965-4

    Article  CAS  PubMed  Google Scholar 

  14. Hancock ML, Preitner N, Quan J, Flanagan JG (2014) MicroRNA-132 is enriched in developing axons, locally regulates Rasa1 mRNA, and promotes axon extension. J Neurosci 34(1):66–78. https://doi.org/10.1523/JNEUROSCI.3371-13.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang Y, Chopp M, Liu XS, Kassis H, Wang X, Li C, An G, Zhang ZG (2015) MicroRNAs in the axon locally mediate the effects of chondroitin sulfate proteoglycans and cGMP on axonal growth. Dev Neurobiol 75(12):1402–1419. https://doi.org/10.1002/dneu.22292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Li S, Wang X, Yun G, Chen C, Wang Y, Liu J, Wen H, Bin Y et al (2015) Let-7 microRNAs regenerate peripheral nerve regeneration by targeting nerve growth factor. Mol Ther 23(3):423–433. https://doi.org/10.1038/mt.2014.220

    Article  CAS  PubMed  Google Scholar 

  17. Zhou S, Shen D, Wang Y et al (2012) microRNA-222 targeting PTEN promotes neurite outgrowth from adult dorsal root ganglion neurons following sciatic nerve transection [published correction appears in PLoS One 7(9). https://doi.org/10.1371/journal.pone.0044768

  18. Wang XW, Li Q, Liu CM, Hall PA, Jiang JJ, Katchis CD, Kang S, Dong BC et al (2018) Lin28 signaling supports mammalian PNS and CNS axon regeneration. Cell Rep 24(10):2540-2552.e6. https://doi.org/10.1016/j.celrep.2018.07.105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhang L, Wang Z, Li B, Xia Z, Wang X, Xiu Y, Zhang Z, Chen C et al (2020) The inhibition of miR-17-5p promotes cortical neuron neurite growth via STAT3/GAP-43 pathway. Mol Biol Rep 47(3):1795–1802. https://doi.org/10.1007/s11033-020-05273-1

    Article  CAS  PubMed  Google Scholar 

  20. Wang Y, Wang H, Li X, Li Y (2016) Epithelial microRNA-9a regulates dendrite growth through Fmi-Gq signaling in drosophila sensory neurons. Dev Neurobiol 76(2):225–237. https://doi.org/10.1002/dneu.22309

    Article  CAS  PubMed  Google Scholar 

  21. Yao C, Wang J, Zhang H, Zhou S, Qian T, Ding F, Xiaosong G, Bin Y (2015) Long non-coding RNA uc.217 regulates neurite outgrowth in dorsal root ganglion neurons following peripheral nerve injury. Eur J Neurosci. 42(1):1718–1725. https://doi.org/10.1111/ejn.12966

    Article  PubMed  Google Scholar 

  22. Corset V, Nguyen-Ba-Charvet KT, Forcet C, Moyse E, Chédotal A, Mehlen P (2000) Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor. Nature 407(6805):747–750. https://doi.org/10.1038/35037600

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Stein E, Zou Y, Poo M, Tessier-Lavigne M (2001) Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation. Science 291(5510):1976–1982. https://doi.org/10.1126/science.1059391

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Wang X, Chen Q, Yi S, Liu Q, Zhang R, Wang P, Qian T, Li S (2019) The microRNAs let-7 and miR-9 down-regulate the axon-guidance genes Ntn1 and Dcc during peripheral nerve regeneration. J Biol Chem 294(10):3489–3500. https://doi.org/10.1074/jbc.RA119.007389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wei W, Wong K, Chen JH, Jiang ZH, Dupuis S, Wu JY, Rao Y (1999) Directional guidance of neuronal migration in the olfactory system by the protein Slit. Nature 400(6742):331–336. https://doi.org/10.1038/22477

    Article  ADS  Google Scholar 

  26. Li HS, Chen JH, Wei W, Fagaly T, Zhou L, Yuan W, Dupuis S, Jiang ZH et al (1999) Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons. Cell 96(6):807–818. https://doi.org/10.1016/s0092-8674(00)80591-7

    Article  CAS  PubMed  Google Scholar 

  27. Nguyen Ba-Charvet KT, Brose K, Ma L, Wang KH, Marillat V, Sotelo C, Tessier-Lavigne M, Chédotal A (2001) Diversity and specificity of actions of Slit2 proteolytic fragments in axon guidance. J Neurosci 21(12):4281–4289. https://doi.org/10.1523/JNEUROSCI.21-12-04281.2001

    Article  CAS  PubMed  Google Scholar 

  28. Kos A, Klein-Gunnewiek T, Meinhardt J, Olde Loohuis NFM, Bokhoven HV, Kaplan BB, Martens GJ, Kolk SM et al (2017) MicroRNA-338 attenuates cortical neuronal outgrowth by modulating the expression of axon guidance genes. Mol Neurobiol 54(5):3439–3452. https://doi.org/10.1007/s12035-016-9925-z

    Article  CAS  PubMed  Google Scholar 

  29. Peng SX, Yao L, Cui C, Zhao HD, Liu CJ, Li YH, Wang LF, Huang SB et al (2017) Semaphorin4D promotes axon regrowth and swimming ability during recovery following zebrafish spinal cord injury. Neuroscience 351:36–46. https://doi.org/10.1016/j.neuroscience.2017.03.030

    Article  CAS  PubMed  Google Scholar 

  30. Sasidharan V, Marepally S, Elliott SA et al (2017) The miR-124 family of microRNAs is crucial for regeneration of the brain and visual system in the planarian Schmidtea mediterranea. Development 144(18):3211–3223. https://doi.org/10.1242/dev.144758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen R, Yang X, Zhang B, Wang S, Bao S, Yun G, Li S (2019) EphA4 negatively regulates myelination by inhibiting schwann cell differentiation in the peripheral nervous system. Front Neurosci 13:1191. https://doi.org/10.3389/fnins.2019.01191

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tang XQ, Tanelian DL, Smith GM (2004) Semaphorin3A inhibits nerve growth factor-induced sprouting of nociceptive afferents in adult rat spinal cord. J Neurosci 24(4):819–827. https://doi.org/10.1523/JNEUROSCI.1263-03.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Han SM, Baig HS, Hammarlund M (2016) Mitochondria localize to injured axons to support regeneration. Neuron 92(6):1308–1323. https://doi.org/10.1016/j.neuron.2016.11.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Neel DV, Basu H, Gunner G, Bergstresser MD, Giadone RM, Chung H, Miao R, Chou V et al (2023) Gasdermin-E mediates mitochondrial damage in axons and neurodegeneration. Neuron 111(8):1222-1240.e9. https://doi.org/10.1016/j.neuron.2023.02.019

    Article  CAS  PubMed  Google Scholar 

  35. Zhou B, Yu P, Lin MY, Sun T, Chen Y, Sheng ZH (2016) Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits. J Cell Biol 214(1):103–119. https://doi.org/10.1083/jcb.201605101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. O’Donnell KC, Vargas ME, Sagasti A (2013) WldS and PGC-1α regulate mitochondrial transport and oxidation state after axonal injury. J Neurosci 33(37):14778–14790. https://doi.org/10.1523/JNEUROSCI.1331-13.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hammarlund M, Nix P, Hauth L, Jorgensen EM, Bastiani M (2009) Axon regeneration requires a conserved MAP kinase pathway. Science 323(5915):802–806. https://doi.org/10.1126/science.1165527

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  38. Shorey M, Stone MC, Mandel J, Rolls MM (2020) Neurons survive simultaneous injury to axons and dendrites and regrow both types of processes in vivo. Dev Biol 465(2):108–118. https://doi.org/10.1016/j.ydbio.2020.07.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Xiong X, Wang X, Ewanek R, Bhat P, Diantonio A, Collins CA (2010) Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury. J Cell Biol 191(1):211–223. https://doi.org/10.1083/jcb.201006039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Shin JE, Cho Y, Beirowski B, Milbrandt J, Cavalli V, DiAntonio A (2012) Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration. Neuron 74(6):1015–1022. https://doi.org/10.1016/j.neuron.2012.04.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Watkins TA, Wang B, Huntwork-Rodriguez S, Yang J, Jiang Z, Eastham-Anderson J, Modrusan Z, Kaminker JS et al (2013) DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury. Proc Natl Acad Sci U S A 110(10):4039–4044. https://doi.org/10.1073/pnas.1211074110

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  42. Jin Y, Zheng B (2019) Multitasking: dual leucine zipper-bearing kinases in neuronal development and stress management. Annu Rev Cell Dev Biol 35:501–521. https://doi.org/10.1146/annurev-cellbio-100617-062644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Farías GG, Guardia CM, De Pace R, Britt DJ, Bonifacino JS (2017) BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon. Proc Natl Acad Sci U S A 114(14):E2955–E2964. https://doi.org/10.1073/pnas.1616363114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wu YE, Huo L, Maeder CI, Feng W, Shen K (2017) BORC regulates the axonal transport of synaptic vesicle precursors by activating ARL-8. Curr Biol 27(17):2569–2578. https://doi.org/10.1016/j.cub.2017.07.013

    Article  CAS  Google Scholar 

  45. Klassen MP, Wu YE, Maeder CI, Nakae I, Cueva JG, Lehrman EK, Tada M, Gengyo-Ando K et al (2010) An Arf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation. Neuron 66(5):710–723. https://doi.org/10.1016/j.neuron.2010.04.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Liz MA, Mar FM, Santos TE, Pimentel HI, Marques AM, Morgado MM, Vieira S, Sousa VF et al (2014) Neuronal deletion of GSK3β increases microtubule speed in the growth cone and enhances axon regeneration via CRMP-2 and independently of MAP1B and CLASP2. BMC Biol 12:47. https://doi.org/10.1186/1741-7007-12-47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wu X, Xu XM (2016) RhoA/Rho kinase in spinal cord injury. Neural Regen Res 11(1):23–27. https://doi.org/10.4103/1673-5374.169601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gumy LF, Katrukha EA, Grigoriev Il, Jaarsma D, Kapitein LC, Akhmanova A, Hoogenraad CC (2017) MAP2 defines a pre-axonal filtering zone to regulate KIF1- versus KIF5-dependent cargo transport in sensory neurons. Neuron 94(2):347-362.e7. https://doi.org/10.1016/j.neuron.2017.03.046

    Article  CAS  PubMed  Google Scholar 

  49. Eva R, Koseki H, Kanamarlapudi V, Fawcett JW (2017) EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment. J Cell Sci 130(21):3663–3675. https://doi.org/10.1242/jcs.207423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sugio S, Nagasawa M, Kojima I, Ishizaki Y, Shibasaki K (2017) Transient receptor potential vanilloid 2 activation by focal mechanical stimulation requires interaction with the actin cytoskeleton and enhances growth cone motility. FASEB J 31(4):1368–1381. https://doi.org/10.1096/fj.201600686RR

    Article  CAS  PubMed  Google Scholar 

  51. Pease ME, McKinnon SJ, Quigley HA, Kerrigan-Baumrind LA, Zack DJ (2000) Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma. Invest Ophthalmol Vis Sci 41(3):764–774

    CAS  PubMed  Google Scholar 

  52. Zhang F, Gu X, Yi S, Xu H (2019) Dysregulated transcription factor TFAP2A after peripheral nerve injury modulated schwann cell phenotype. Neurochem Res 44(12):2776–2785. https://doi.org/10.1007/s11064-019-02898-y

    Article  ADS  CAS  PubMed  Google Scholar 

  53. Garrett LB, Kuijper JL, Ardourel D, Wolfson MF, Debrot S, Mudri S, Kleist K, Griffin LL et al (2023) Povetacicept, an enhanced dual APRIL/BAFF antagonist that modulates B lymphocytes and pathogenic autoantibodies for the treatment of lupus and other B cell-related autoimmune diseases. Arthritis Rheumatol 75(7):1187–1202. https://doi.org/10.1002/art.42462

    Article  CAS  PubMed  Google Scholar 

  54. Ho PTB, Clark IM, Le LTT (2022) MicroRNA-based diagnosis and therapy. Int J Mol Sci 23(13):7167. https://doi.org/10.3390/ijms23137167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Guthrie S (1997) Axon guidance: netrin receptors are revealed. Curr Biol 7(1):R6–R9. https://doi.org/10.1016/s0960-9822(06)00007-8

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  56. Prieur DS, Francius C, Gaspar P, Mason CA, Rebsam A (2023) Semaphorin-6D and plexin-A1 act in a non-cell-autonomous manner to position and target retinal ganglion cell axons. J Neurosci 43(32):5769–5778. https://doi.org/10.1523/JNEUROSCI.0072-22.2023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Murcia-Belmonte V, Erskine L (2019) Wiring the binocular visual pathways. Int J Mol Sci 20(13):3282. https://doi.org/10.3390/ijms20133282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bélisle JM, Levin LA, Costantino S (2012) High-content neurite development study using optically patterned substrates. PLoS ONE 7(4):e35911. https://doi.org/10.1371/journal.pone.0035911

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wang H, Ozaki T, Shamim Hossain M, Nakamura Y, Kamijo T, Xue X, Nakagawara A (2008) A newly identified dependence receptor UNC5H4 is induced during DNA damage-mediated apoptosis and transcriptional target of tumor suppressor p53. Biochem Biophys Res Commun 370(4):594–598. https://doi.org/10.1016/j.bbrc.2008.03.152

    Article  CAS  PubMed  Google Scholar 

  60. Petit A, Sellers DL, Liebl DJ, Tessier-Lavigne M, Kennedy TE, Horner PJ (2007) Adult spinal cord progenitor cells are repelled by netrin-1 in the embryonic and injured adult spinal cord. Proc Natl Acad Sci U S A 104(45):17837–17842. https://doi.org/10.1073/pnas.0703240104

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  61. Koohini Z, Koohini Z, Teimourian S (2019) Slit/Robo signaling pathway in cancer; a new stand point for cancer treatment. Pathol Oncol Res 25(4):1285–1293. https://doi.org/10.1007/s12253-018-00568-y

    Article  CAS  PubMed  Google Scholar 

  62. Klein R (2009) Bidirectional modulation of synaptic functions by Eph/ephrin signaling. Nat Neurosci 12(1):15–20. https://doi.org/10.1038/nn.2231

    Article  CAS  PubMed  Google Scholar 

  63. Yang JS, Wei HX, Chen PP, Wu G (2018) Roles of Eph/ephrin bidirectional signaling in central nervous system injury and recovery. Exp Ther Med 15(3):2219–2227. https://doi.org/10.3892/etm.2018.5702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Fiore L, Olmos-Carreño CL, Medori M, Spelzini G, Sanchez V, Scicolone G (2022) Neurospheres obtained from the ciliary margin of the chicken eye possess positional values and retinal ganglion cells differentiated from them respond to EphA/ephrin-A system. Exp Eye Res 217:108965. https://doi.org/10.1016/j.exer.2022.108965

    Article  CAS  PubMed  Google Scholar 

  65. Limoni G, Niquille M (2021) Semaphorins and plexins in central nervous system patterning: the key to it all? Curr Opin Neurobiol 66:224–232. https://doi.org/10.1016/j.conb.2020.12.014

    Article  CAS  PubMed  Google Scholar 

  66. Moreau-Fauvarque C, Kumanogoh A, Camand E, Jaillard C, Barbin G, Boquet I, Love EC, Jones Y et al (2003) The transmembrane semaphorin Sema4D/CD100, an inhibitor of axonal growth, is expressed on oligodendrocytes and upregulated after CNS lesion. J Neurosci 23(27):9229–9239. https://doi.org/10.1523/JNEUROSCI.23-27-09229.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Goldberg JL, Vargas ME, Wang JT, Mandemakers W, Oster SF, Sretavan DW, Barres BA (2004) An oligodendrocyte lineage-specific semaphorin, Sema5A, inhibits axon growth by retinal ganglion cells. J Neurosci 24(21):4989–4999. https://doi.org/10.1523/JNEUROSCI.4390-03.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Murillo B, Mendes SM (2018) Neuronal intrinsic regenerative capacity: the impact of microtubule organization and axonal transport. Dev Neurobiol 78(10):952–959. https://doi.org/10.1002/dneu.22602

    Article  PubMed  Google Scholar 

  69. Mar FM, Simões AR, Leite S, Morgado MM, Santos TE, Rodrigo IS, Teixeira CA, Misgeld T et al (2014) CNS axons globally increase axonal transport after peripheral conditioning. J Neurosci 34(17):5965–5970. https://doi.org/10.1523/JNEUROSCI.4680-13.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ferguson SM (2018) Axonal transport and maturation of lysosomes. Curr Opin Neurobiol 51:45–51. https://doi.org/10.1016/j.conb.2018.02.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Sleigh JN, Rossor AM, Fellows AD, Tosolini AP, Schiavo G (2019) Axonal transport and neurological disease. Nat Rev Neurol 15(12):691–703. https://doi.org/10.1038/s41582-019-0257-2

    Article  PubMed  Google Scholar 

  72. Twelvetrees AE, Pernigo S, Sanger A, Guedes-Dias P, Schiavo G, Steiner RA, Dodding MP, Holzbaur ELF (2016) The dynamic localization of cytoplasmic dynein in neurons is driven by kinesin-1. Neuron 90(5):1000–1015. https://doi.org/10.1016/j.neuron.2016.04.046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Maday S, Twelvetrees AE, Moughamian AJ, Holzbaur EL (2014) Axonal transport: cargo-specific mechanisms of motility and regulation. Neuron 84(2):292–309. https://doi.org/10.1016/j.neuron.2014.10.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Terenzio M, Schiavo G, Fainzilber M (2017) Compartmentalized signaling in neurons: from cell biology to neuroscience. Neuron 96(3):667–679. https://doi.org/10.1016/j.neuron.2017.10.015

    Article  CAS  PubMed  Google Scholar 

  75. Reck-Peterson SL, Redwine WB, Vale RD, Carter AP (2018) The cytoplasmic dynein transport machinery and its many cargoes [published correction appears in Nat Rev Mol Cell Biol. 2018 May 8]. Nat Rev Mol Cell Biol 19(6):382–398. https://doi.org/10.1038/s41580-018-0004-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Villarroel-Campos D, Schiavo G, Lazo OM (2018) The many disguises of the signalling endosome. FEBS Lett 592(21):3615–3632. https://doi.org/10.1002/1873-3468.13235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pita-Thomas W, Mahar M, Joshi A, Gan D, Cavalli V (2019) HDAC5 promotes optic nerve regeneration by activating the mTOR pathway. Exp Neurol 317:271–283. https://doi.org/10.1016/j.expneurol.2019.03.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Ghosh-Roy A, Wu Z, Goncharov A, Jin Y, Chisholm AD (2010) Calcium and cyclic AMP promote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase. J Neurosci 30(9):3175–3183. https://doi.org/10.1523/JNEUROSCI.5464-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Saito A, Cavalli V (2016) Signaling over distances. Mol Cell Proteomics 15(2):382–393. https://doi.org/10.1074/mcp.R115.052753

    Article  CAS  PubMed  Google Scholar 

  80. Lewis TL Jr, Turi GF, Kwon SK, Losonczy A, Polleux F (2016) Progressive decrease of mitochondrial motility during maturation of cortical axons in vitro and in vivo. Curr Biol 26(19):2602–2608. https://doi.org/10.1016/j.cub.2016.07.064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wu YE, Huo L, Maeder CI, Feng W, Shen K (2013) The balance between capture and dissociation of presynaptic proteins controls the spatial distribution of synapses. Neuron 78(6):994–1011. https://doi.org/10.1016/j.neuron.2013.04.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Pease SE, Segal RA (2014) Preserve and protect: maintaining axons within functional circuits. Trends Neurosci 37(10):572–582. https://doi.org/10.1016/j.tins.2014.07.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Forbes LH, Andrews MR (2017) Restoring axonal localization and transport of transmembrane receptors to promote repair within the injured CNS: a critical step in CNS regeneration. Neural Regen Res 12(1):27–30. https://doi.org/10.4103/1673-5374.198968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Palmieri M, Frati A, Santoro A, Frati P, Fineschi V, Pesce A (2021) Diffuse axonal injury: clinical prognostic factors, molecular experimental models and the impact of the trauma related oxidative stress .An extensive review concerning milestones and advances. Int J Mol Sci 22(19):10865. https://doi.org/10.3390/ijms221910865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Prior R, Van Helleputte L, Benoy V, Van Den Bosch L (2017) Defective axonal transport: a common pathological mechanism in inherited and acquired peripheral neuropathies. Neurobiol Dis 105:300–320. https://doi.org/10.1016/j.nbd.2017.02.009

    Article  CAS  PubMed  Google Scholar 

  86. Blanquie O, Bradke F (2018) Cytoskeleton dynamics in axon regeneration. Curr Opin Neurobiol 51:60–69. https://doi.org/10.1016/j.conb.2018.02.024

    Article  CAS  PubMed  Google Scholar 

  87. Zhao Y, Xuanyuan W, Chen X, Li J, Tian C, Chen J, Xiao C, Zhong G et al (2020) Calcineurin signaling mediates disruption of the axon initial segment cytoskeleton after injury. iScience 23(2):100880. https://doi.org/10.1016/j.isci.2020.100880

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  88. Verma P, Chierzi S, Codd AM, Campbell DS, Meyer R L, Holt CE, Fawcett JW (2005) Axonal protein synthesis and degradation are necessary for efficient growth cone regeneration. J Neurosci 25(2):331–342. https://doi.org/10.1523/JNEUROSCI.3073-04.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Cafferty WBJ, Gardiner NJ, Gavazzi I, Powell J, McMahon SB, Heath JK, Munson J, Cohen J et al (2001) Leukemia inhibitory factor determines the growth status of injured adult sensory neurons. J Neurosci 21(18):7161–7170. https://doi.org/10.1523/JNEUROSCI.21-18-07161.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Miao T, Dongsheng W, Zhang Y, Bo X, Subang MC, Wang P, Richardson PM (2006) Suppressor of cytokine signaling-3 suppresses the ability of activated signal transducer and activator of transcription-3 to stimulate neurite growth in rat primary sensory neurons. J Neurosci 26(37):9512–9519. https://doi.org/10.1523/JNEUROSCI.2160-06.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. McCormick LE, Gupton SL (2020) Mechanistic advances in axon pathfinding. Curr Opin Cell Biol 63:11–19. https://doi.org/10.1016/j.ceb.2019.12.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Dias DO, Kalkitsas J, Kelahmetoglu Y, Estrada CP, Tatarishvili J, Holl D, Jansson L, Banitalebi S et al (2021) Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions. Nat Commun 12(1):5501. https://doi.org/10.1038/s41467-021-25585-5

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  93. Yiu G, He Z (2006) Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 7(8):617–627. https://doi.org/10.1038/nrn1956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Li Y, Andereggen L, Yuki K et al (2017) Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration. Proc Natl Acad Sci U S A 114(2):E209–E218. https://doi.org/10.1073/pnas.1616811114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Mahar M, Cavalli V (2018) Intrinsic mechanisms of neuronal axon regeneration. Nat Rev Neurosci 19(6):323–337. https://doi.org/10.1038/s41583-018-0001-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Weng YL, An R, Cassin J, Joseph J, Mi R, Wang C, Zhong C, Jin SG et al (2017) An intrinsic epigenetic barrier for functional axon regeneration. Neuron 94(2):337–346. https://doi.org/10.1016/j.neuron.2017.03.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. He Z, Jin Y (2016) Intrinsic control of axon regeneration. Neuron 90(3):437–451. https://doi.org/10.1016/j.neuron.2016.04.022

    Article  CAS  PubMed  Google Scholar 

  98. Danilov CA, Steward O (2015) Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice. Exp Neurol 266:147–160. https://doi.org/10.1016/j.expneurol.2015.02.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Boczek T, Cameron EG, Wendou Y, Xia X, Shah SH, Chabeco BC, Galvao J, Nahmou M et al (2019) Regulation of neuronal survival and axon growth by a perinuclear cAMP compartment. J Neurosci 39(28):5466–5480. https://doi.org/10.1523/JNEUROSCI.2752-18.2019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Priscilla R, Szaro BG (2019) Comparisons of SOCS mRNA and protein levels in Xenopus provide insights into optic nerve regenerative success. Brain Res 1704:150–160. https://doi.org/10.1016/j.brainres.2018.10.012

    Article  CAS  PubMed  Google Scholar 

  101. Chen B, Li Y, Bin Y, Zhang Z, Brommer B, Williams PR, Liu Y, Hegarty SV et al (2018) Reactivation of dormant relay pathways in injured spinal cord by KCC2 manipulations. Cell 174(6):1599. https://doi.org/10.1016/j.cell.2018.08.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Mokalled MH, Patra C, Dickson AL, Endo T, Stainier DY, Poss KD (2016) Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish. Science 354(6312):630–634. https://doi.org/10.1126/science.aaf2679

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  103. Muralidharan H, Baas PW (2019) Mitotic motor KIFC1 is an organizer of microtubules in the axon. J Neurosci 39(20):3792–3811. https://doi.org/10.1523/JNEUROSCI.3099-18.2019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Pereira L, Aeschimann F, Wang C et al (2019) Timing mechanism of sexually dimorphic nervous system differentiation. Elife 8:e42078. https://doi.org/10.7554/eLife.42078

    Article  PubMed  PubMed Central  Google Scholar 

  105. Nieuwenhuis B, Haenzi B, Andrews MR, Verhaagen J, Fawcett JW (2018) Integrins promote axonal regeneration after injury of the nervous system. Biol Rev Camb Philos Soc 93(3):1339–1362. https://doi.org/10.1111/brv.12398

    Article  PubMed  PubMed Central  Google Scholar 

  106. Lutz AB, Lucas TA, Carson GA, Caneda C, Zhou L, Barres BA, Buckwalter MS, Sloan SA (2022) An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury. J Neuroinflammation 19(1):105. https://doi.org/10.1186/s12974-022-02462-6

    Article  CAS  Google Scholar 

  107. Jessen KR, Mirsky R (2016) The repair Schwann cell and its function in regenerating nerves. J Physiol 594(13):3521–3531. https://doi.org/10.1113/JP270874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Bosch-Queralt M, Fledrich R, Stassart RM (2023) Schwann cell functions in peripheral nerve development and repair. Neurobiol Dis 176:105952. https://doi.org/10.1016/j.nbd.2022.105952

    Article  CAS  PubMed  Google Scholar 

  109. Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15(3):178–196. https://doi.org/10.1038/nrm3758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Clements MP, Byrne E, Camarillo LF, Guerrero ALC, Zakka L, Ashraf A, Burden JJ, Khadayate S et al (2017) The wound microenvironment reprograms Schwann cells to invasive mesenchymal-like cells to drive peripheral nerve regeneration. Neuron 96(1):98–114. https://doi.org/10.1016/j.neuron.2017.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Szepanowski F, Szepanowski LP, Mausberg AK, Kleinschnitz C, Kieseier BC, Stettner M (2018) Lysophosphatidic acid propagates post-injury Schwann cell dedifferentiation through LPA1 signaling. Neurosci Lett 662:136–141. https://doi.org/10.1016/j.neulet.2017.10.023

    Article  CAS  PubMed  Google Scholar 

  112. Ying Z, Pan C, Shao T, Liu L, Li L, Guo D, Zhang S, Yuan T et al (2018) Mixed lineage kinase domain-like protein MLKL breaks down myelin following nerve injury. Mol Cell 72(3):457-468.e5. https://doi.org/10.1016/j.molcel.2018.09.011

    Article  CAS  PubMed  Google Scholar 

  113. Yang DP, Kim J, Syed N, Tung YJ, Bhaskaran A, Mindos T, Mirsky R, Jessen KR et al (2012) p38 MAPK activation promotes denervated Schwann cell phenotype and functions as a negative regulator of Schwann cell differentiation and myelination. J Neurosci 32(21):7158–7168. https://doi.org/10.1523/JNEUROSCI.5812-11.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Mindos T, Dun XP, North K, Doddrell RDS, Schulz A, Edwards P, Russell J, Gray B et al (2017) Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity. J Cell Biol 216(2):495–510. https://doi.org/10.1083/jcb.201606052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Ahrendsen JT, Harlow DE, Finseth LT, Bourne JN, Hickey SP, Gould EA, Culp CM, Macklin WB (2018) The protein tyrosine phosphatase Shp2 regulates oligodendrocyte differentiation and early myelination and contributes to timely remyelination. J Neurosci 38(4):787–802. https://doi.org/10.1523/JNEUROSCI.2864-16.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Bremer M, Fröb F, Kichko T, Reeh P, Tamm ER, Suter U, Wegner M (2011) Sox10 is required for Schwann-cell homeostasis and myelin maintenance in the adult peripheral nerve. Glia 59(7):1022–1032. https://doi.org/10.1002/glia.21173

    Article  PubMed  Google Scholar 

  117. Chung WS, Clarke LE, Wang GX, Stafford BK, Sher A, Chakraborty C, Joung J, Foo LC et al (2013) Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 504(7480):394–400. https://doi.org/10.1038/nature12776

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  118. Brosius Lutz A, Chung WS, Sloan SA et al (2017) Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury. Proc Natl Acad Sci U S A 114(38):E8072–E8080. https://doi.org/10.1073/pnas.1710566114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Stratton JA, Holmes A, Rosin NL, Sinha S, Vohra M, Burma NE, Trang T, Midha R et al (2018) Macrophages regulate Schwann cell maturation after nerve injury. Cell Rep 24(10):2561-2572.e6. https://doi.org/10.1016/j.celrep.2018.08.004

    Article  CAS  PubMed  Google Scholar 

  120. Tsarouchas TM, Wehner D, Cavone L, Munir T, Keatinge M, Lambertus M, Underhill A, Barrett T et al (2018) Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration. Nat Commun 9(1):4670. https://doi.org/10.1038/s41467-018-07036-w

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  121. Büttner R, Schulz A, Reuter M et al (2018) Inflammaging impairs peripheral nerve maintenance and regeneration. Aging Cell 17(6):e12833. https://doi.org/10.1111/acel.12833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Zhou T, Zheng Y, Sun L, Badea SR, Jin Y, Liu Y, Rolfe AJ, Sun H et al (2019) Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury. Nat Neurosci 22(3):421–435. https://doi.org/10.1038/s41593-018-0324-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Weinger JG, Brosnan CF, Loudig O, Goldberg MF, Macian F, Arnett HA, Prieto AL, Tsiperson V et al (2011) Loss of the receptor tyrosine kinase Axl leads to enhanced inflammation in the CNS and delayed removal of myelin debris during experimental autoimmune encephalomyelitis. J Neuroinflammation 8:49. https://doi.org/10.1186/1742-2094-8-49

    Article  PubMed  PubMed Central  Google Scholar 

  124. Brushart TM, Aspalter M, Griffin JW, Redett R, Hameed H, Zhou C, Wright M, Vyas A et al (2013) Schwann cell phenotype is regulated by axon modality and central-peripheral location, and persists in vitro. Exp Neurol 247:272–281. https://doi.org/10.1016/j.expneurol.2013.05.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Dun XP, Parkinson DB (2017) Role of Netrin-1 signaling in nerve regeneration. Int J Mol Sci 18(3):491. https://doi.org/10.3390/ijms18030491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Ko KR, Lee J, Lee D, Nho B, Kim S (2018) Hepatocyte growth factor (HGF) promotes peripheral nerve regeneration by activating repair Schwann cells. Sci Rep 8(1):8316. https://doi.org/10.1038/s41598-018-26704-x

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  127. Vallières N, Barrette B, Wang LX, Bélanger E, Thiry L, Schneider MR, Filali M, Côté D et al (2017) Betacellulin regulates schwann cell proliferation and myelin formation in the injured mouse peripheral nerve. Glia 65(4):657–669. https://doi.org/10.1002/glia.23119

    Article  PubMed  Google Scholar 

  128. Yu B, Zhou S, Wang Y et al (2012) miR-221 and miR-222 promote Schwann cell proliferation and migration by targeting LASS2 after sciatic nerve injury. J Cell Sci 125(Pt 11):2675–2683. https://doi.org/10.1242/jcs.098996

    Article  CAS  PubMed  Google Scholar 

  129. Parrinello S, Napoli I, Ribeiro S, Digby PW, Fedorova M, Parkinson DB, Doddrell RDS, Nakayama M et al (2010) EphB signaling directs peripheral nerve regeneration through Sox2-dependent Schwann cell sorting. Cell 143(1):145–155. https://doi.org/10.1016/j.cell.2010.08.039

    Article  CAS  PubMed  Google Scholar 

  130. Robering JW, Gebhardt L, Wolf K, Kühn H, Kremer AE, Fischer MJM (2019) Lysophosphatidic acid activates satellite glia cells and Schwann cells. Glia 67(5):999–1012. https://doi.org/10.1002/glia.23585

    Article  PubMed  Google Scholar 

  131. Yi S, Wang S, Zhao Q, Yao C, Yun G, Liu J, Xiaosong G, Li S (2016) miR-sc3, a novel MicroRNA, promotes Schwann cell proliferation and migration by targeting Astn1. Cell Transplant 25(5):973–982. https://doi.org/10.3727/096368916X690520

    Article  PubMed  Google Scholar 

  132. Neumann E, Brandenburger T, Santana-Varela S, Deenen R, Köhrer K, Bauer I, Hermanns H, Wood JN et al (2016) MicroRNA-1-associated effects of neuron-specific brain-derived neurotrophic factor gene deletion in dorsal root ganglia. Mol Cell Neurosci 75:36–43. https://doi.org/10.1016/j.mcn.2016.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Gu Y, Chen C, Yi S et al (2015) miR-sc8 inhibits Schwann cell proliferation and migration by targeting Egfr. PLoS ONE 10(12):e0145185. https://doi.org/10.1371/journal.pone.0145185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Tedeschi A, Dupraz S, Laskowski CJ, Xue J, Ulas T, Beyer M, Schultze JL et al (2016) The calcium channel subunit Alpha2delta2 suppresses axon regeneration in the adult CNS. Neuron 92(2):419–434. https://doi.org/10.1016/j.neuron.2016.09.026

    Article  CAS  PubMed  Google Scholar 

  135. He X, Zhang L, Queme LF, Liu X, Andrew L, Waclaw RR, Dong X, Zhou Wenhao et al (2018) A histone deacetylase 3-dependent pathway delimits peripheral myelin growth and functional regeneration. Nat Med 24(3):338–351. https://doi.org/10.1038/nm.4483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Wen-Feng S, Fan W, Jin ZH, Yun G, Chen YT, Fei Y, Chen H, Wang YX et al (2019) Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury. Glia 67(1):78–90. https://doi.org/10.1002/glia.23527

    Article  Google Scholar 

  137. Wang H, Zhang P, Yu J, Zhang F, Dai W, Yi S (2019) Matrix metalloproteinase 7 promoted Schwann cell migration and myelination after rat sciatic nerve injury. Mol Brain 12(1):101. https://doi.org/10.1186/s13041-019-0516-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Quintes S, Brinkmann BG, Ebert M, Fröb F, Kungl T, Arlt FA, Tarabykin V, Huylebroeck D et al (2016) Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair. Nat Neurosci 19(8):1050–1059. https://doi.org/10.1038/nn.4321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Miyamoto Y, Torii T, Tago K, Tanoue A, Takashima S, Yamauchi J (2018) BIG1/Arfgef1 and Arf1 regulate the initiation of myelination by Schwann cells in mice. Sci Adv 4(4):eaar4471. https://doi.org/10.1126/sciadv.aar4471

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  140. Doddrell RD, Dun XP, Moate RM, Jessen KR, Mirsky R, Parkinson DB (2012) Regulation of Schwann cell differentiation and proliferation by the Pax-3 transcription factor. Glia 60(9):1269–1278. https://doi.org/10.1002/glia.22346

    Article  PubMed  PubMed Central  Google Scholar 

  141. Yi S, Liu Q, Wang X, Qian T, Wang H, Zha G, Jun Y, Wang P et al (2019) Tau modulates Schwann cell proliferation, migration and differentiation following peripheral nerve injury. J Cell Sci 132(6):jcs222059. https://doi.org/10.1242/jcs.222059

    Article  CAS  PubMed  Google Scholar 

  142. Chen R, Yang X, Zhang B, Wang S, Bao S, Yun G, Li S (2019) EphA4 negatively regulates myelination by inhibiting Schwann cell differentiation in the peripheral nervous system. Front Neurosci 13:1191. https://doi.org/10.3389/fnins.2019.01191

    Article  PubMed  PubMed Central  Google Scholar 

  143. Byrne M (2020) The link between autotomy and CNS regeneration: echinoderms as non-model species for regenerative biology. BioEssays 42(3):e1900219. https://doi.org/10.1002/bies.201900219

    Article  PubMed  Google Scholar 

  144. Carr MJ, Johnston AP (2017) Schwann cells as drivers of tissue repair and regeneration. Curr Opin Neurobiol 47:52–57. https://doi.org/10.1016/j.conb.2017.09.003

    Article  CAS  PubMed  Google Scholar 

  145. Zimmermann J, Emrich M, Krauthausen M, Saxe S, Nitsch L, Heneka MT, Campbell IL, Müller M (2018) IL-17A promotes granulocyte infiltration, myelin loss, microglia activation, and behavioral deficits during cuprizone-induced demyelination. Mol Neurobiol 55(2):946–957. https://doi.org/10.1007/s12035-016-0368-3

    Article  CAS  PubMed  Google Scholar 

  146. Chen P, Cescon M, Zuccolotto G, Nobbio L, Colombelli C, Filaferro M, Giovanni Vitale M, Feltri L et al (2015) Collagen VI regulates peripheral nerve regeneration by modulating macrophage recruitment and polarization. Acta Neuropathol 129(1):97–113. https://doi.org/10.1007/s00401-014-1369-9

    Article  CAS  PubMed  Google Scholar 

  147. Cattin AL, Burden JJ, Van Emmenis L, Mackenzie FE, Hoving JJA, Calavia NG, Guo Y, McLaughlin M et al (2015) Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves. Cell 162(5):1127–1139. https://doi.org/10.1016/j.cell.2015.07.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Cho Y, Shin JE, Ewan EE, Oh YM, Pita-Thomas W, Cavalli V (2015) Activating injury-responsive genes with hypoxia enhances axon regeneration through neuronal HIF-1α. Neuron 88(4):720–734. https://doi.org/10.1016/j.neuron.2015.09.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Jessen KR, Mirsky R (2022) The role of c-Jun and autocrine signaling loops in the control of repair schwann cells and regeneration. Front Cell Neurosci 15:820216. https://doi.org/10.3389/fncel.2021.820216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Gordon T (2016) Electrical stimulation to enhance axon regeneration after peripheral nerve injuries in animal models and humans. Neurotherapeutics 13(2):295–310. https://doi.org/10.1007/s13311-015-0415-1

    Article  PubMed  PubMed Central  Google Scholar 

  151. Yao C, Wang Y, Zhang H, Feng W, Wang Q, Shen D, Qian T, Liu F et al (2018) lncRNA TNXA-PS1 modulates Schwann cells by functioning as a competing endogenous RNA following nerve injury. J Neurosci 38(29):6574–6585. https://doi.org/10.1523/JNEUROSCI.3790-16.2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Hossain S, de la Cruz-Morcillo MA, Sanchez-Prieto R, Almazan G (2012) Mitogen-activated protein kinase p38 regulates Krox-20 to direct Schwann cell differentiation and peripheral myelination. Glia 60(7):1130–1144. https://doi.org/10.1002/glia.22340

    Article  PubMed  Google Scholar 

  153. Zuchero JB, Barres BA (2015) Glia in mammalian development and disease. Development 142(22):3805–3809. https://doi.org/10.1242/dev.129304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Laha B, Stafford BK, Huberman AD (2017) Regenerating optic pathways from the eye to the brain. Science 356(6342):1031–1034. https://doi.org/10.1126/science.aal5060

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  155. Anderson MA, Burda JE, Ren Y, Ao Y, O’Shea TM, Kawaguchi R, Coppola G, Khakh BS et al (2016) Astrocyte scar formation aids central nervous system axon regeneration. Nature 532(7598):195–200. https://doi.org/10.1038/nature17623

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  156. Tedeschi A, Omura T, Costigan M (2017) CNS repair and axon regeneration: using genetic variation to determine mechanisms. Exp Neurol 287(Pt 3):409–422. https://doi.org/10.1016/j.expneurol.2016.05.004

    Article  PubMed  Google Scholar 

  157. Yu B, Gu X (2019) Combination of biomaterial transplantation and genetic enhancement of intrinsic growth capacities to promote CNS axon regeneration after spinal cord injury. Front Med 13(2):131–137. https://doi.org/10.1007/s11684-018-0642-z

    Article  PubMed  Google Scholar 

  158. Lim JHA, Stafford BK, Nguyen PL, Lien BV, Wang C, Zukor K, He Z, Huberman AD (2016) Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat Neurosci 19(8):1073–1084. https://doi.org/10.1038/nn.4340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Guo X, Snider WD, Chen B (2016) GSK3β regulates AKT-induced central nervous system axon regeneration via an eIF2Bε-dependent, mTORC1-independent pathway. Elife 5:e11903. https://doi.org/10.7554/eLife.11903

    Article  PubMed  PubMed Central  Google Scholar 

  160. David S, Aguayo AJ (1981) Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science 214(4523):931–933. https://doi.org/10.1126/science.6171034

    Article  ADS  CAS  PubMed  Google Scholar 

  161. Fawcett JW (2018) The paper that restarted modern central nervous system axon regeneration research. Trends Neurosci 41(5):239–242. https://doi.org/10.1016/j.tins.2018.02.012

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  162. Kaplan A, Morquette B, Kroner A, Leong SY, Madwar C, Sanz R, Banerjee SL, Antel J et al (2017) Small-molecule stabilization of 14–3-3 protein-protein interactions stimulates axon regeneration. Neuron 93(5):1082-1093.e5. https://doi.org/10.1016/j.neuron.2017.02.018

    Article  CAS  PubMed  Google Scholar 

  163. Yang Y, Hao-Yu X, Deng QW, Guo-Hui W, Zeng X, Jin H, Wang LJ, Lai BQ et al (2021) Electroacupuncture facilitates the integration of a grafted TrkC-modified mesenchymal stem cell-derived neural network into transected spinal cord in rats via increasing neurotrophin-3. CNS Neurosci Ther 27(7):776–791. https://doi.org/10.1111/cns.13638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Shah SH, Goldberg JL (2018) The role of axon transport in neuroprotection and regeneration. Dev Neurobiol 78(10):998–1010. https://doi.org/10.1002/dneu.22630

    Article  PubMed  PubMed Central  Google Scholar 

  165. Sun H, Fu S, Cui S, Yin X, Sun X, Qi X, Cui K, Wang J et al (2020) Development of a CRISPR-SaCas9 system for projection- and function-specific gene editing in the rat brain. Sci Adv 6(12):6687. https://doi.org/10.1126/sciadv.aay6687

    Article  ADS  CAS  Google Scholar 

  166. Anjum A, Yazid MD, Fauzi Daud M, Idris J, Ng AMH, Selvi Naicker A, Ismail OHR, Athi Kumar RK et al (2020) Spinal Cord Injury: Pathophysiology, multimolecular interactions, and underlying recovery mechanisms. Int J Mol Sci. 21(20):7533. https://doi.org/10.3390/ijms21207533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Cui Y, Wang Y, Song X et al (2021) Brain endothelial PTEN/AKT/NEDD4-2/MFSD2A axis regulates blood-brain barrier permeability. Cell Rep 36(1):109327. https://doi.org/10.1016/j.celrep.2021.109327

    Article  CAS  PubMed  Google Scholar 

  168. Nie D, Chen Z, Ebrahimi-Fakhari D, Di Nardo A, Julich K, Robson VK, Cheng Y-C, Woolf CJ et al (2015) The stress-induced Atf3-gelsolin cascade underlies dendritic spine deficits in neuronal models of tuberous sclerosis complex. J Neurosci 35(30):10762–10772. https://doi.org/10.1523/JNEUROSCI.4796-14.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Min HS, Kim HJ, Naito M, Ogura S, Toh K, Hayashi K, Kim BS, Fukushima S et al (2020) Systemic brain delivery of antisense oligonucleotides across the blood-brain barrier with a glucose-coated polymeric nanocarrier. Angew Chem Int Ed Engl 59(21):8173–8180. https://doi.org/10.1002/anie.201914751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the National Nature Science Foundation of China (Grant number: 32200800 and 31970968) and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant number: KYCX22_3331).

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  1. Wenshuang Wu and Jing Zhang contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China

    Wenshuang Wu, Jing Zhang, Yu Chen, Shiying Li & Xinghui Wang

  2. Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China

    Qianqian Chen & Fuchao Zhang

  3. School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, 410208, China

    Qianyan Liu

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  1. Wenshuang Wu
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For research articles, WW and JZ were involved in the conception and design of the manuscript. YC, QC, QL, and FZ drafted and revised the review by literature retrieval and reference acquisition. SL and XW performed manuscript review and gave final approval of the version to be published. All authors have read and approved the final manuscript.

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Correspondence to Shiying Li or Xinghui Wang.

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Wu, W., Zhang, J., Chen, Y. et al. Genes in Axonal Regeneration. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04049-z

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