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The Notch Signaling Pathway Regulates Differentiation of NG2 Cells into Oligodendrocytes in Demyelinating Diseases

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Abstract

NG2 cells are highly proliferative glial cells that can self-renew or differentiate into oligodendrocytes, promoting remyelination. Following demyelination, the proliferative and differentiation potentials of NG2 cells increase rapidly, enhancing their differentiation into functional myelinating cells. Levels of the transcription factors Olig1 and Olig2 increase during the differentiation of NG2 cells and play important roles in the development and repair of oligodendrocytes. However, the ability to generate new oligodendrocytes is hampered by injury-related factors (e.g., myelin fragments, Wnt and Notch signaling components), leading to failed differentiation and maturation of NG2 cells into oligodendrocytes. Here, we review Notch signaling as a negative regulator of oligodendrocyte differentiation and discuss the extracellular ligands, intracellular pathways, and key transcription factors involved.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

aTf:

Apotransferrin

CNS:

Central nervous system

CC:

Corpus callosum

ET-1:

Endothelin 1

FGF2:

Fibroblast growth factor 2

MS:

Multiple sclerosis

NICD:

Notch intracellular domain

OLs:

Oligodendrocytes

TGF-β1:

Transforming growth factor β1

TR4:

Testicular orphan receptor 4

References

  • Ahrendsen JT, Grewal HS, Hickey SP, Culp CM, Gould EA, Shimizu T et al (2016) Juvenile striatal white matter is resistant to ischemia-induced damage. Glia 64(11):1972–1986

    PubMed  PubMed Central  Google Scholar 

  • Aparicio E, Mathieu P, Pereira LM, Almeira GM, Adamo AM (2013) The Notch signaling pathway: its role in focal CNS demyelination and apotransferrin-induced remyelination. J Neurochem 127(6):819–836

    CAS  PubMed  Google Scholar 

  • Azim K, Butt AM (2011) GSK3beta negatively regulates oligodendrocyte differentiation and myelination in vivo. Glia 59(4):540–553

    PubMed  Google Scholar 

  • Belachew S, Chittajallu R, Aguirre AA, Yuan X, Kirby M, Anderson S et al (2003) Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J Cell Biol 161(1):169–186

    CAS  PubMed  PubMed Central  Google Scholar 

  • Blanchard B, Heurtaux T, Garcia C, Moll NM, Caillava C, Grandbarbe L et al (2013) Tocopherol derivative TFA-12 promotes myelin repair in experimental models of multiple sclerosis. J Neurosci 33(28):11633–11642

    CAS  PubMed  PubMed Central  Google Scholar 

  • Boda E, Vigano F, Rosa P, Fumagalli M, Labat-Gest V, Tempia F et al (2011) The GPR17 receptor in NG2 expressing cells: focus on in vivo cell maturation and participation in acute trauma and chronic damage. Glia 59(12):1958–1973

    PubMed  Google Scholar 

  • Boulanger JJ, Messier C (2017) Oligodendrocyte progenitor cells are paired with GABA neurons in the mouse dorsal cortex: unbiased stereological analysis. Neuroscience 362:127–140

    CAS  PubMed  Google Scholar 

  • Chen BY, Zheng MH, Chen Y, Du YL, Sun XL, Zhang X et al (2015) Myeloid-specific blockade of Notch signaling by RBP-J knockout attenuates spinal cord injury accompanied by compromised inflammation response in mice. Mol Neurobiol 52(3):1378–1390

    CAS  PubMed  Google Scholar 

  • Chew LJ, Shen W, Ming X, Senatorov VJ, Chen HL, Cheng Y et al (2011) SRY-box containing gene 17 regulates the Wnt/beta-catenin signaling pathway in oligodendrocyte progenitor cells. J Neurosci 31(39):13921–13935

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chew LJ, Ming X, McEllin B, Dupree J, Hong E, Catron M et al (2019) Sox17 regulates a program of oligodendrocyte progenitor cell expansion and differentiation during development and repair. Cell Rep 29(10):3173–3186

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chittajallu R, Aguirre A, Gallo V (2004) NG2-positive cells in the mouse white and grey matter display distinct physiological properties. J Physiol 561(Pt 1):109–122

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cohen P, Goedert M (2004) GSK3 inhibitors: development and therapeutic potential. Nat Rev Drug Discov 3(6):479–487

    CAS  PubMed  Google Scholar 

  • Dai ZM, Sun S, Wang C, Huang H, Hu X, Zhang Z et al (2014) Stage-specific regulation of oligodendrocyte development by Wnt/beta-catenin signaling. J Neurosci 34(25):8467–8473

    PubMed  PubMed Central  Google Scholar 

  • Dawson MR, Polito A, Levine JM, Reynolds R (2003) NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Mol Cell Neurosci 24(2):476–488

    CAS  PubMed  Google Scholar 

  • Diers-Fenger M, Kirchhoff F, Kettenmann H, Levine JM, Trotter J (2001) AN2/NG2 protein-expressing glial progenitor cells in the murine CNS: isolation, differentiation, and association with radial glia. Glia 34(3):213–228

    CAS  PubMed  Google Scholar 

  • Dou CL, Levine JM (1994) Inhibition of neurite growth by the NG2 chondroitin sulfate proteoglycan. J Neurosci 14(12):7616–7628

    CAS  PubMed  PubMed Central  Google Scholar 

  • Du M, Tan Y, Liu G, Liu L, Cao F, Liu J et al (2017) Effects of the Notch signalling pathway on hyperoxia-induced immature brain damage in newborn mice. Neurosci Lett 653:220–227

    CAS  PubMed  Google Scholar 

  • Fan H, Zhao JG, Yan JQ, Du GQ, Fu QZ, Shi J et al (2018) Effect of Notch1 gene on remyelination in multiple sclerosis in mouse models of acute demyelination. J Cell Biochem 119(11):9284–9294

    CAS  PubMed  Google Scholar 

  • Fancy SP, Baranzini SE, Zhao C, Yuk DI, Irvine KA, Kaing S et al (2009) Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes Dev 23(13):1571–1585

    CAS  PubMed  PubMed Central  Google Scholar 

  • Faux CH, Turnley AM, Epa R, Cappai R, Bartlett PF (2001) Interactions between fibroblast growth factors and Notch regulate neuronal differentiation. J Neurosci 21(15):5587–5596

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gadea A, Aguirre A, Haydar TF, Gallo V (2009) Endothelin-1 regulates oligodendrocyte development. J Neurosci 29(32):10047–10062

    CAS  PubMed  PubMed Central  Google Scholar 

  • Galimberti D, Macmurray J, Scalabrini D, Fenoglio C, De Riz M, Comi C et al (2011) GSK3beta genetic variability in patients with multiple sclerosis. Neurosci Lett 497(1):46–48

    CAS  PubMed  Google Scholar 

  • Gaudet AD, Fonken LK (2018) Glial cells shape pathology and repair after spinal cord injury. Neurotherapeutics 15(3):554–577

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ge W, Martinowich K, Wu X, He F, Miyamoto A, Fan G et al (2002) Notch signaling promotes astrogliogenesis via direct CSL-mediated glial gene activation. J Neurosci Res 69(6):848–860

    CAS  PubMed  Google Scholar 

  • Genoud S, Lappe-Siefke C, Goebbels S, Radtke F, Aguet M, Scherer SS et al (2002) Notch1 control of oligodendrocyte differentiation in the spinal cord. J Cell Biol 158(4):709–718

    CAS  PubMed  PubMed Central  Google Scholar 

  • Givogri MI, Costa RM, Schonmann V, Silva AJ, Campagnoni AT, Bongarzone ER (2002) Central nervous system myelination in mice with deficient expression of Notch1 receptor. J Neurosci Res 67(3):309–320

    CAS  PubMed  Google Scholar 

  • Gomez PL, Rodriguez D, Adamo AM, Mathieu PA (2018) TGF-beta pro-oligodendrogenic effects on adult SVZ progenitor cultures and its interaction with the Notch signaling pathway. Glia 66(2):396–412

    Google Scholar 

  • Grandbarbe L, Bouissac J, Rand M, Hrabe DAM, Artavanis-Tsakonas S, Mohier E (2003) Delta-Notch signaling controls the generation of neurons/glia from neural stem cells in a stepwise process. Development 130(7):1391–1402

    CAS  PubMed  Google Scholar 

  • Gray GE, Mann RS, Mitsiadis E, Henrique D, Carcangiu ML, Banks A et al (1999) Human ligands of the Notch receptor. Am J Pathol 154(3):785–794

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hammond TR, Gadea A, Dupree J, Kerninon C, Nait-Oumesmar B, Aguirre A et al (2014) Astrocyte-derived endothelin-1 inhibits remyelination through notch activation. Neuron 81(3):588–602

    CAS  PubMed  PubMed Central  Google Scholar 

  • Heinrich C, Bergami M, Gascon S, Lepier A, Vigano F, Dimou L et al (2014) Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex. Stem Cell Rep 3(6):1000–1014

    CAS  Google Scholar 

  • Hesp ZC, Yoseph RY, Suzuki R, Jukkola P, Wilson C, Nishiyama A et al (2018) Proliferating NG2-cell-dependent angiogenesis and scar formation alter axon growth and functional recovery after spinal cord injury in mice. J Neurosci 38(6): 1366–1382

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hill RA, Patel KD, Medved J, Reiss AM, Nishiyama A (2013) NG2 cells in white matter but not gray matter proliferate in response to PDGF. J Neurosci 33(36):14558–14566

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hu QD, Ang BT, Karsak M, Hu WP, Cui XY, Duka T et al (2003) F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Cell 115(2):163–175

    CAS  PubMed  Google Scholar 

  • Hu QD, Ma QH, Gennarini G, Xiao ZC (2006) Cross-talk between F3/contactin and Notch at axoglial interface: a role in oligodendrocyte development. Dev Neurosci 28(1–2):25–33

    CAS  PubMed  Google Scholar 

  • Huang W, Bai X, Stopper L, Catalin B, Cartarozzi LP, & Scheller A et al (2018) During development NG2 glial cells of the spinal cord are restricted to the oligodendrocyte lineage, but generate astrocytes upon acute injury. Neuroscience 385:154–165

    CAS  PubMed  Google Scholar 

  • Jarriault S, Le Bail O, Hirsinger E, Pourquie O, Logeat F, Strong CF et al (1998) Delta-1 activation of notch-1 signaling results in HES-1 transactivation. Mol Cell Biol 18(12):7423–7431

    CAS  PubMed  PubMed Central  Google Scholar 

  • John GR, Shankar SL, Shafit-Zagardo B, Massimi A, Lee SC, Raine CS et al (2002) Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med 8(10):1115–1121

    CAS  PubMed  Google Scholar 

  • Jones LL, Yamaguchi Y, Stallcup WB, Tuszynski MH (2002) NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. J Neurosci 22(7):2792–2803

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jurynczyk M, Jurewicz A, Bielecki B, Raine CS, Selmaj K (2005) Inhibition of Notch signaling enhances tissue repair in an animal model of multiple sclerosis. J Neuroimmunol 170(1–2):3–10

    CAS  PubMed  Google Scholar 

  • Khazaei M, Ahuja CS, Nakashima H, Nagoshi N, Li L, Wang J et al (2020) GDNF rescues the fate of neural progenitor grafts by attenuating Notch signals in the injured spinal cord in rodents. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aau3538

    Article  PubMed  Google Scholar 

  • Kockeritz L, Doble B, Patel S, Woodgett JR (2006) Glycogen synthase kinase-3–an overview of an over-achieving protein kinase. Curr Drug Targets 7(11):1377–1388

    CAS  PubMed  Google Scholar 

  • Kondo T, Raff M (2000) Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation. Development 127(14):2989–2998

    CAS  PubMed  Google Scholar 

  • Langseth AJ, Munji RN, Choe Y, Huynh T, Pozniak CD, Pleasure SJ (2010) Wnts influence the timing and efficiency of oligodendrocyte precursor cell generation in the telencephalon. J Neurosci 30(40):13367–13372

    CAS  PubMed  PubMed Central  Google Scholar 

  • Levine JM (1994) Increased expression of the NG2 chondroitin-sulfate proteoglycan after brain injury. J Neurosci 14(8):4716–4730

    CAS  PubMed  PubMed Central  Google Scholar 

  • Levine J (2016) The reactions and role of NG2 glia in spinal cord injury. Brain Res 1638(Pt B):199–208

    CAS  PubMed  Google Scholar 

  • Levine JM, Reynolds R, Fawcett JW (2001) The oligodendrocyte precursor cell in health and disease. Trends Neurosci 24(1):39–47

    CAS  PubMed  Google Scholar 

  • Li R, Zhang P, Zhang M, Yao Z (2020) The roles of neuron-NG2 glia synapses in promoting oligodendrocyte development and remyelination. Cell Tissue Res 381(1):43–53

    PubMed  Google Scholar 

  • Liang T, Zhu L, Gao W, Gong M, Ren J, Yao H et al (2017) Coculture of endothelial progenitor cells and mesenchymal stem cells enhanced their proliferation and angiogenesis through PDGF and Notch signaling. FEBS Open Bio 7(11):1722–1736

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lindsell CE, Boulter J, DiSibio G, Gossler A, Weinmaster G (1996) Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development. Mol Cell Neurosci 8(1):14–27

    CAS  PubMed  Google Scholar 

  • Liu C, Li D, Lv C, Gao Z, Qi Y, Wu H et al (2020) Activation of the Notch signaling pathway and cellular localization of notch signaling molecules in the spinal cord of SOD1-G93A ALS model mice. Neuroscience 432:84–93

    CAS  PubMed  Google Scholar 

  • Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4(5):399–415

    CAS  PubMed  Google Scholar 

  • Marumo T, Takagi Y, Muraki K, Hashimoto N, Miyamoto S, Tanigaki K (2013) Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke. Neurosci Res 75(3):204–209

    CAS  PubMed  Google Scholar 

  • Mathieu PA, Almeira GM, Rodriguez D, Gomez PL, Calcagno ML, Adamo AM (2019) Demyelination-remyelination in the central nervous system: ligand-dependent participation of the Notch signaling pathway. Toxicol Sci 171:172–192

    CAS  Google Scholar 

  • Matsumoto H, Kumon Y, Watanabe H, Ohnishi T, Shudou M, Chuai M et al (2008) Accumulation of macrophage-like cells expressing NG2 proteoglycan and Iba1 in ischemic core of rat brain after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab 28(1):149–163

    CAS  PubMed  Google Scholar 

  • Miller RH (2002) Regulation of oligodendrocyte development in the vertebrate CNS. Prog Neurobiol 67(6):451–467

    CAS  PubMed  Google Scholar 

  • Mohapel P, Frielingsdorf H, Haggblad J, Zachrisson O, Brundin P (2005) Platelet-derived growth factor (PDGF-BB) and brain-derived neurotrophic factor (BDNF) induce striatal neurogenesis in adult rats with 6-hydroxydopamine lesions. Neuroscience 132(3):767–776

    CAS  PubMed  Google Scholar 

  • Muller T, Grandbarbe L, Morga E, Heuschling P, Luu B (2004) Tocopherol long chain fatty alcohols decrease the production of TNF-alpha and NO radicals by activated microglial cells. Bioorg Med Chem Lett 14(24):6023–6026

    CAS  PubMed  Google Scholar 

  • Nagarajan B, Harder A, Japp A, Haberlein F, Mingardo E, Kleinert H et al (2020) CNS myelin protein 36K regulates oligodendrocyte differentiation through Notch. Glia 68(3):509–527

    PubMed  Google Scholar 

  • Nasoohi S, Hemmati AA, Moradi F, Ahmadiani A (2012) The gamma-secretase blocker DAPT impairs recovery from lipopolysaccharide-induced inflammation in rat brain. Neuroscience 210:99–109

    CAS  PubMed  Google Scholar 

  • Nonneman A, Criem N, Lewandowski SA, Nuyts R, Thal DR, Pfrieger FW et al (2018) Astrocyte-derived Jagged-1 mitigates deleterious Notch signaling in amyotrophic lateral sclerosis. Neurobiol Dis 119:26–40

    CAS  PubMed  Google Scholar 

  • Ohtsuka T, Ishibashi M, Gradwohl G, Nakanishi S, Guillemot F, Kageyama R (1999) Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation. EMBO J 18(8):2196–2207

    CAS  PubMed  PubMed Central  Google Scholar 

  • Palagani V, El KM, Kossatz U, Bozko P, Muller MR, Manns MP et al (2012) Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/EpCAM+ cells are inhibited by gamma-secretase inhibitor IX. PLoS ONE 7(10):e46514

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pantoni L, Garcia JH, Gutierrez JA (1996) Cerebral white matter is highly vulnerable to ischemia. Stroke 27(9):1641–1646

    CAS  PubMed  Google Scholar 

  • Park HC, Appel B (2003) Delta-Notch signaling regulates oligodendrocyte specification. Development 130(16):3747–3755

    CAS  PubMed  Google Scholar 

  • Parras CM, Hunt C, Sugimori M, Nakafuku M, Rowitch D, Guillemot F (2007) The proneural gene Mash1 specifies an early population of telencephalic oligodendrocytes. J Neurosci 27(16):4233–4242

    CAS  PubMed  PubMed Central  Google Scholar 

  • Philips T, Bento-Abreu A, Nonneman A, Haeck W, Staats K, Geelen V et al (2013) Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis. Brain 136(Pt 2):471–482

    PubMed  PubMed Central  Google Scholar 

  • Pietersen CY, Mauney SA, Kim SS, Passeri E, Lim MP, Rooney RJ et al (2014) Molecular profiles of parvalbumin-immunoreactive neurons in the superior temporal cortex in schizophrenia. J Neurogenet 28(1–2):70–85

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pivonkova H, Benesova J, Butenko O, Chvatal A, Anderova M (2010) Impact of global cerebral ischemia on K+ channel expression and membrane properties of glial cells in the rat hippocampus. Neurochem Int 57(7):783–794

    CAS  PubMed  Google Scholar 

  • Qian D, Li L, Rong Y, Liu W, Wang Q, Zhou Z et al (2019) Blocking Notch signal pathway suppresses the activation of neurotoxic A1 astrocytes after spinal cord injury. Cell Cycle 18(21):3010–3029

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schmitz T, Ritter J, Mueller S, Felderhoff-Mueser U, Chew LJ, Gallo V (2011) Cellular changes underlying hyperoxia-induced delay of white matter development. J Neurosci 31(11):4327–4344

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sim FJ, McClain CR, Schanz SJ, Protack TL, Windrem MS, Goldman SA (2011) CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells. Nat Biotechnol 29(10):934–941

    CAS  PubMed  PubMed Central  Google Scholar 

  • Simon C, Gotz M, Dimou L (2011) Progenitors in the adult cerebral cortex: cell cycle properties and regulation by physiological stimuli and injury. Glia 59(6):869–881

    PubMed  Google Scholar 

  • Snyder JL, Kearns CA, Appel B (2012) Fbxw7 regulates Notch to control specification of neural precursors for oligodendrocyte fate. Neural Dev 7:15

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sohn J, Natale J, Chew LJ, Belachew S, Cheng Y, Aguirre A et al (2006) Identification of Sox17 as a transcription factor that regulates oligodendrocyte development. J Neurosci 26(38):9722–9735

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D et al (2009) Common variants conferring risk of schizophrenia. Nature 460(7256):744–747

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stidworthy MF, Genoud S, Li WW, Leone DP, Mantei N, Suter U et al (2004) Notch1 and Jagged1 are expressed after CNS demyelination, but are not a major rate-determining factor during remyelination. Brain 127(Pt 9):1928–1941

    PubMed  Google Scholar 

  • Tan AM, Colletti M, Rorai AT, Skene JH, Levine JM (2006) Antibodies against the NG2 proteoglycan promote the regeneration of sensory axons within the dorsal columns of the spinal cord. J Neurosci 26(18):4729–4739

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka K, Nogawa S, Ito D, Suzuki S, Dembo T, Kosakai A et al (2001) Activation of NG2-positive oligodendrocyte progenitor cells during post-ischemic reperfusion in the rat brain. NeuroReport 12(10):2169–2174

    CAS  PubMed  Google Scholar 

  • Tanigaki K, Nogaki F, Takahashi J, Tashiro K, Kurooka H, Honjo T (2001) Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate. Neuron 29(1):45–55

    CAS  PubMed  Google Scholar 

  • Tawk M, Makoukji J, Belle M, Fonte C, Trousson A, Hawkins T et al (2011) Wnt/beta-catenin signaling is an essential and direct driver of myelin gene expression and myelinogenesis. J Neurosci 31(10):3729–3742

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tran AP, Warren PM, Silver J (2018) The biology of regeneration failure and success after spinal cord injury. Physiol Rev 98(2):881–917

    CAS  PubMed  PubMed Central  Google Scholar 

  • Uranova N, Orlovskaya D, Vikhreva O, Zimina I, Kolomeets N, Vostrikov V et al (2001) Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull 55(5):597–610

    CAS  PubMed  Google Scholar 

  • Wang A, He BP (2009) Characteristics and functions of NG2 cells in normal brain and neuropathology. Neurol Res 31(2):144–150

    PubMed  Google Scholar 

  • Wang S, Sdrulla AD, DiSibio G, Bush G, Nofziger D, Hicks C et al (1998) Notch receptor activation inhibits oligodendrocyte differentiation. Neuron 21(1):63–75

    PubMed  Google Scholar 

  • Wang HN, Liu GH, Zhang RG, Xue F, Wu D, Chen YC et al (2015) Quetiapine ameliorates schizophrenia-like behaviors and protects myelin integrity in cuprizone intoxicated mice: the involvement of Notch signaling pathway. Int J Neuropsychopharmacol. https://doi.org/10.1093/ijnp/pyv088

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang C, Zhang CJ, Martin BN, Bulek K, Kang Z, Zhao J et al (2017) IL-17 induced NOTCH1 activation in oligodendrocyte progenitor cells enhances proliferation and inflammatory gene expression. Nat Commun 8:15508

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu X, Zhang A, Zhu Y, He W, Di W, Fang Y et al (2018) MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-kappaB and PI3K-Akt pathways. J Cell Physiol 234(1):904–914

    PubMed  Google Scholar 

  • Yang Z, Suzuki R, Daniels SB, Brunquell CB, Sala CJ, Nishiyama A (2006) NG2 glial cells provide a favorable substrate for growing axons. J Neurosci 26(14):3829–3839

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yoon K, Nery S, Rutlin ML, Radtke F, Fishell G, Gaiano N (2004) Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in telencephalic progenitors. J Neurosci 24(43):9497–9506

    CAS  PubMed  PubMed Central  Google Scholar 

  • Young WJ, Smith SM, Chang C (1997) Induction of the intronic enhancer of the human ciliary neurotrophic factor receptor (CNTFRalpha) gene by the TR4 orphan receptor. A member of steroid receptor superfamily. J Biol Chem 272(5):3109–3116

    CAS  PubMed  Google Scholar 

  • Yuen TJ, Johnson KR, Miron VE, Zhao C, Quandt J, Harrisingh MC et al (2013) Identification of endothelin 2 as an inflammatory factor that promotes central nervous system remyelination. Brain 136(Pt 4):1035–1047

    PubMed  PubMed Central  Google Scholar 

  • Zaucker A, Mercurio S, Sternheim N, Talbot WS, Marlow FL (2013) notch3 is essential for oligodendrocyte development and vascular integrity in zebrafish. Dis Model Mech 6(5):1246–1259

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Chen YT, Xie S, Wang L, Lee YF, Chang SS et al (2007) Loss of testicular orphan receptor 4 impairs normal myelination in mouse forebrain. Mol Endocrinol 21(4):908–920

    CAS  PubMed  Google Scholar 

  • Zhang Y, Argaw AT, Gurfein BT, Zameer A, Snyder BJ, Ge C et al (2009) Notch1 signaling plays a role in regulating precursor differentiation during CNS remyelination. Proc Natl Acad Sci USA 106(45):19162–19167

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhang H, Wang L, Jiang W, Xu H, Xiao L et al (2012) Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination. Schizophr Res 138(1):8–17

    PubMed  Google Scholar 

  • Zhang R, Chopp M, Zhang ZG (2013) Oligodendrogenesis after cerebral ischemia. Front Cell Neurosci 7:201

    PubMed  PubMed Central  Google Scholar 

  • Zhou YX, Armstrong RC (2007) Interaction of fibroblast growth factor 2 (FGF2) and notch signaling components in inhibition of oligodendrocyte progenitor (OP) differentiation. Neurosci Lett 421(1):27–32

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou YX, Flint NC, Murtie JC, Le TQ, Armstrong RC (2006) Retroviral lineage analysis of fibroblast growth factor receptor signaling in FGF2 inhibition of oligodendrocyte progenitor differentiation. Glia 54(6):578–590

    PubMed  PubMed Central  Google Scholar 

  • Zhu X, Bergles DE, Nishiyama A (2008) NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development 135(1):145–157

    CAS  PubMed  Google Scholar 

  • Zhu X, Hill RA, Dietrich D, Komitova M, Suzuki R, Nishiyama A (2011) Age-dependent fate and lineage restriction of single NG2 cells. Development 138(4):745–753

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC; Grant No. 81860225).

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  1. Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Zheng Street, Nanchang, 330006, Jiangxi, People’s Republic of China

    Chengcai Li, Zhiping Xie, Zelong Xing, Huaxin Zhu, Wu Zhou, Shenke Xie, Zhixiong Zhang & Mei-Hua Li

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  1. Chengcai Li
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LCC, XZP, XZL, ZHX, ZW, XSK, ZZX, and LMH reviewed the literature and drafted the manuscript. LCC and LMH critically revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mei-Hua Li.

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Li, C., Xie, Z., Xing, Z. et al. The Notch Signaling Pathway Regulates Differentiation of NG2 Cells into Oligodendrocytes in Demyelinating Diseases. Cell Mol Neurobiol 42, 1–11 (2022). https://doi.org/10.1007/s10571-021-01089-0

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  • DOI: https://doi.org/10.1007/s10571-021-01089-0

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