Skip to main content
Log in

The Neural Stem Cell Microenvironment: Focusing on Axon Guidance Molecules and Myelin-Associated Factors

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Neural stem cells (NSCs) could produce various cell phenotypes in the subventricular zone (SVZ) and dentate gyrus of the hippocampus in the central nervous system (CNS), where neurogenesis has been determined to occur. The extracellular microenvironment also influences the behaviors of NSCs during development and at CNS injury sites. Our previous study indicates that myelin, a component of the CNS, could regulate the differentiation of NSCs in vitro. Recent reports have implicated three myelin-derived inhibitors, NogoA, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp), as well as several axon guidance molecules as regulators of NSC survival, proliferation, migration, and differentiation. However, the molecular mechanisms underlying the behavior of NSCs are not fully understood. In this study, we summarize the current literature on the effects of different extrinsic factors on NSCs and discuss possible mechanisms, as well as future possible clinical applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ader M, Schachner M, Bartsch U (2001) Transplantation of neural precursor cells into the dysmyelinated CNS of mutant mice deficient in the myelin‐associated glycoprotein and Fyn tyrosine kinase. Eur J Neurosci 14:561–566

    CAS  PubMed  Google Scholar 

  • Afshari FT, Kappagantula S, Fawcett JW (2009) Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury. Expert Rev Mol Med 11:e37

    PubMed  Google Scholar 

  • Alvarez-Buylla A, Lim DA (2004) For the long run: maintaining germinal niches in the adult brain. Neuron 41:683–686

    CAS  PubMed  Google Scholar 

  • Andrews W, Barber M, Hernadez-Miranda LR, Xian J, Rakic S, Sundaresan V, Rabbitts TH, Pannell R, Rabbitts P, Thompson H, Erskine L, Murakami F, Parnavelas JG (2008) The role of Slit-Robo signaling in the generation, migration and morphological differentiation of cortical interneurons. Dev Biol 313:648–658

    CAS  PubMed  Google Scholar 

  • Aoki M, Yamashita T, Tohyama M (2004) EphA receptors direct the differentiation of mammalian neural precursor cells through a mitogen-activated protein kinase-dependent pathway. J Biol Chem 279:32643–32650

    CAS  PubMed  Google Scholar 

  • Atwal JK, Pinkston-Gosse J, Syken J, Stawicki S, Wu Y, Shatz C, Tessier-Lavigne M (2008) PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 322:967–970

    CAS  PubMed  Google Scholar 

  • Bagnard D, Sainturet N, Meyronet D, Perraut M, Miehe M, Roussel G, Aunis D, Belin MF, Thomasset N (2004) Differential MAP kinases activation during semaphorin3A-induced repulsion or apoptosis of neural progenitor cells. Mol Cell Neurosci 25:722–731

    CAS  PubMed  Google Scholar 

  • Bloch-Gallego E, Ezan F, Tessier-Lavigne M, Sotelo C (1999) Floor plate and netrin-1 are involved in the migration and survival of inferior olivary neurons. J Neurosci 19:4407–4420

    CAS  PubMed  Google Scholar 

  • Borrell V, Cardenas A, Ciceri G, Galceran J, Flames N, Pla R, Nobrega-Pereira S, Garcia-Frigola C, Peregrin S, Zhao Z, Ma L, Tessier-Lavigne M, Marin O (2012) Slit/Robo signaling modulates the proliferation of central nervous system progenitors. Neuron 76:338–352

    CAS  PubMed Central  PubMed  Google Scholar 

  • Busch SA, Silver J (2007) The role of extracellular matrix in CNS regeneration. Curr Opin Neurobiol 17:120–127

    CAS  PubMed  Google Scholar 

  • Chakravarthy B, Gaudet C, Menard M, Atkinson T, Brown L, Laferla FM, Armato U, Whitfield J (2010) Amyloid-beta peptides stimulate the expression of the p75(NTR) neurotrophin receptor in SHSY5Y human neuroblastoma cells and AD transgenic mice. J Alzheimers Dis 19:915–925

    CAS  PubMed  Google Scholar 

  • Chilton JK (2006) Molecular mechanisms of axon guidance. Dev Biol 292:13–24

    CAS  PubMed  Google Scholar 

  • Choi HW, Kim JS, Choi S, Hong YJ, Kim MJ, Seo HG, Do JT (2014) Neural stem cells differentiated from iPS cells spontaneously regain pluripotency. Stem Cells 32:2596–2604

    CAS  PubMed  Google Scholar 

  • Christian KM, Song H, Ming G-l (2013) Functions and dysfunctions of adult hippocampal neurogenesis. Annu Rev Neurosci 37:243–262

    Google Scholar 

  • Chumley MJ, Catchpole T, Silvany RE, Kernie SG, Henkemeyer M (2007) EphB receptors regulate stem/progenitor cell proliferation, migration, and polarity during hippocampal neurogenesis. J Neurosci 27:13481–13490

    CAS  PubMed  Google Scholar 

  • Conover JC, Doetsch F, Garcia-Verdugo JM, Gale NW, Yancopoulos GD, Alvarez-Buylla A (2000) Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Nat Neurosci 3:1091–1097

    CAS  PubMed  Google Scholar 

  • Crespo D, Asher RA, Lin R, Rhodes KE, Fawcett JW (2007) How does chondroitinase promote functional recovery in the damaged CNS? Exp Neurol 206:159–171

    CAS  PubMed  Google Scholar 

  • Daadi MM, Davis AS, Arac A, Li Z, Maag A-L, Bhatnagar R, Jiang K, Sun G, Wu JC, Steinberg GK (2010) Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic–ischemic brain injury. Stroke 41:516–523

    PubMed  Google Scholar 

  • De Wit J, De Winter F, Klooster J, Verhaagen J (2005) Semaphorin 3A displays a punctate distribution on the surface of neuronal cells and interacts with proteoglycans in the extracellular matrix. Mol Cell Neurosci 29:40–55

    PubMed  Google Scholar 

  • DeBellard ME, Tang S, Mukhopadhyay G, Shen YJ, Filbin MT (1996) Myelin-associated glycoprotein inhibits axonal regeneration from a variety of neurons via interaction with a sialoglycoprotein. Mol Cell Neurosci 7:89–101

    CAS  PubMed  Google Scholar 

  • del Valle K, Theus MH, Bethea JR, Liebl DJ, Ricard J (2011) Neural progenitors proliferation is inhibited by EphB3 in the developing subventricular zone. Int J Dev Neurosci 29:9–14

    PubMed Central  PubMed  Google Scholar 

  • Depaepe V, Suarez-Gonzalez N, Dufour A, Passante L, Gorski JA, Jones KR, Ledent C, Vanderhaeghen P (2005) Ephrin signalling controls brain size by regulating apoptosis of neural progenitors. Nature 435:1244–1250

    CAS  PubMed  Google Scholar 

  • Dickendesher TL, Baldwin KT, Mironova YA, Koriyama Y, Raiker SJ, Askew KL, Wood A, Geoffroy CG, Zheng B, Liepmann CD, Katagiri Y, Benowitz LI, Geller HM, Giger RJ (2012) NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci 15:703–712

    CAS  PubMed Central  PubMed  Google Scholar 

  • Domeniconi M, Cao Z, Spencer T, Sivasankaran R, Wang KC, Nikulina E, Kimura N, Cai H, Deng K, Gao Y, He Z, Filbin MT (2002) Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 35:283–290

    CAS  PubMed  Google Scholar 

  • Faigle R, Song H (2013) Signaling mechanisms regulating adult neural stem cells and neurogenesis. Biochim Biophys Acta (BBA)-Gen Sub 1830:2435–2448

    CAS  Google Scholar 

  • Fujita Y, Yamashita T (2014) Axon growth inhibition by RhoA/ROCK in the central nervous system. Front Neurosci 8.

  • Genander M, Halford MM, Xu NJ, Eriksson M, Yu Z, Qiu Z, Martling A, Greicius G, Thakar S, Catchpole T, Chumley MJ, Zdunek S, Wang C, Holm T, Goff SP, Pettersson S, Pestell RG, Henkemeyer M, Frisen J (2009) Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression. Cell 139:679–692

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gervasi NM, Kwok JC, Fawcett JW (2008) Role of extracellular factors in axon regeneration in the CNS: implications for therapy. Regen Med 3:907–923

    PubMed  Google Scholar 

  • Goh ELK, Ma D, Ming G-L, Song H (2003) Adult neural stem cells and repair of the adult central nervous system. J Hematother Stem Cell Res 12:671–679

    PubMed  Google Scholar 

  • Goldshmit Y, McLenachan S, Turnley A (2006) Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Res Rev 52:327–345

    CAS  PubMed  Google Scholar 

  • Gu WL, Fu SL, Wang YX, Li Y, Lu HZ, Xu XM, Lu PH (2009) Chondroitin sulfate proteoglycans regulate the growth, differentiation and migration of multipotent neural precursor cells through the integrin signaling pathway. BMC Neurosci 10:128

    PubMed Central  PubMed  Google Scholar 

  • Hakanen J, Duprat S, Salminen M (2011) Netrin1 is required for neural and glial precursor migrations into the olfactory bulb. Dev Biol 355:101–114

    CAS  PubMed  Google Scholar 

  • Hara Y, Nomura T, Yoshizaki K, Frisen J, Osumi N (2010) Impaired hippocampal neurogenesis and vascular formation in ephrin-A5-deficient mice. Stem Cells 28:974–983

    CAS  PubMed  Google Scholar 

  • Harburg GC, Hinck L (2011) Navigating breast cancer: axon guidance molecules as breast cancer tumor suppressors and oncogenes. J Mammary Gland Biol Neoplasia 16:257–270

    PubMed Central  PubMed  Google Scholar 

  • Hayano Y, Sasaki K, Ohmura N, Takemoto M, Maeda Y, Yamashita T, Hata Y, Kitada K, Yamamoto N (2014) Netrin-4 regulates thalamocortical axon branching in an activity-dependent fashion. Proc Natl Acad Sci U S A 111:15226–15231

    CAS  PubMed Central  PubMed  Google Scholar 

  • He N, Jin WL, Lok KH, Wang Y, Yin M, Wang ZJ (2013) Amyloid-beta(1–42) oligomer accelerates senescence in adult hippocampal neural stem/progenitor cells via formylpeptide receptor 2. Cell Death Dis 4:e924

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hedgecock EM, Norris CR (1997) Netrins evoke mixed reactions in motile cells. Trends Genet 13:251–253

    CAS  PubMed  Google Scholar 

  • Hermann DM, Peruzzotti-Jametti L, Schlechter J, Bernstock JD, Doeppner TR, Pluchino S (2014) Neural precursor cells in the ischemic brain - integration, cellular crosstalk, and consequences for stroke recovery. Front Cell Neurosci 8:291

    PubMed Central  PubMed  Google Scholar 

  • Holmberg J, Armulik A, Senti KA, Edoff K, Spalding K, Momma S, Cassidy R, Flanagan JG, Frisen J (2005) Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis. Genes Dev 19:462–471

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hou T, Shi Y, Cheng S, Yang X, Li L, Xiao C (2010) Nogo-A expresses on neural stem cell surface. Int J Neurosci 120:201–205

    CAS  PubMed  Google Scholar 

  • Huang JY, Wang YX, Gu WL, Fu SL, Li Y, Huang LD, Zhao Z, Hang Q, Zhu HQ, Lu PH (2012) Expression and function of myelin-associated proteins and their common receptor NgR on oligodendrocyte progenitor cells. Brain Res 1437:1–15

    CAS  PubMed  Google Scholar 

  • Itoh T, Satou T, Hashimoto S, Ito H (2005) Isolation of neural stem cells from damaged rat cerebral cortex after traumatic brain injury. NeuroReport 16:1687–1691

    PubMed  Google Scholar 

  • Jensen PL (2000) Eph receptors and ephrins. Stem Cells 18:63–64

    CAS  PubMed  Google Scholar 

  • Jing X, Miwa H, Sawada T, Nakanishi I, Kondo T, Miyajima M, Sakaguchi K (2012) Ephrin-A1-mediated dopaminergic neurogenesis and angiogenesis in a rat model of Parkinson’s disease. PLoS One 7:e32019

    CAS  PubMed Central  PubMed  Google Scholar 

  • Julian L, Olson MF (2014) Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases 5:e29846

    PubMed Central  PubMed  Google Scholar 

  • Kantor DB, Chivatakarn O, Peer KL, Oster SF, Inatani M, Hansen MJ, Flanagan JG, Yamaguchi Y, Sretavan DW, Giger RJ, Kolodkin AL (2004) Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans. Neuron 44:961–975

    CAS  PubMed  Google Scholar 

  • Katakowski M, Zhang Z, deCarvalho AC, Chopp M (2005) EphB2 induces proliferation and promotes a neuronal fate in adult subventricular neural precursor cells. Neurosci Lett 385:204–209

    CAS  PubMed  Google Scholar 

  • Kazanis I, ffrench-Constant, C (2011) Extracellular matrix and the neural stem cell niche. Dev Neurobiol 71:1006–1017

    CAS  PubMed  Google Scholar 

  • Kearns SM, Laywell ED, Kukekov VK, Steindler DA (2003) Extracellular matrix effects on neurosphere cell motility. Exp Neurol 182:240–244

    CAS  PubMed  Google Scholar 

  • Keino-Masu K, Masu M, Hinck L, Leonardo ED, Chan SS, Culotti JG, Tessier-Lavigne M (1996) Deleted in Colorectal Cancer (DCC) encodes a netrin receptor. Cell 87:175–185

    CAS  PubMed  Google Scholar 

  • Ketschek AR, Haas C, Gallo G, Fischer I (2012) The roles of neuronal and glial precursors in overcoming chondroitin sulfate proteoglycan inhibition. Exp Neurol 235:627–637

    CAS  PubMed Central  PubMed  Google Scholar 

  • Khodosevich K, Watanabe Y, Monyer H (2011) EphA4 preserves postnatal and adult neural stem cells in an undifferentiated state in vivo. J Cell Sci 124:1268–1279

    CAS  PubMed  Google Scholar 

  • Klagsbrun M, Eichmann A (2005) A role for axon guidance receptors and ligands in blood vessel development and tumor angiogenesis. Cytokine Growth Factor Rev 16:535–548

    CAS  PubMed  Google Scholar 

  • Koeberle PD, Bahr M (2004) Growth and guidance cues for regenerating axons: where have they gone? J Neurobiol 59:162–180

    CAS  PubMed  Google Scholar 

  • Kottis V, Thibault P, Mikol D, Xiao ZC, Zhang R, Dergham P, Braun PE (2002) Oligodendrocyte‐myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth. J Neurochem 82:1566–1569

    CAS  PubMed  Google Scholar 

  • Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033

    CAS  PubMed  Google Scholar 

  • Kwak YD, Brannen CL, Qu T, Kim HM, Dong X, Soba P, Majumdar A, Kaplan A, Beyreuther K, Sugaya K (2006) Amyloid precursor protein regulates differentiation of human neural stem cells. Stem Cells Dev 15:381–389

    CAS  PubMed  Google Scholar 

  • Lepore AC, Fischer I (2005) Lineage-restricted neural precursors survive, migrate, and differentiate following transplantation into the injured adult spinal cord. Exp Neurol 194:230–242

    CAS  PubMed  Google Scholar 

  • Li X, Su H, Fu QL, Guo J, Lee DH, So KF, Wu W (2011) Soluble NgR fusion protein modulates the proliferation of neural progenitor cells via the Notch pathway. Neurochem Res 36:2363–2372

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liu H, Ng CE, Tang BL (2002) Nogo-A expression in mouse central nervous system neurons. Neurosci Lett 328:257–260

    CAS  PubMed  Google Scholar 

  • Liu BP, Cafferty WB, Budel SO, Strittmatter SM (2006) Extracellular regulators of axonal growth in the adult central nervous system. Philos Trans R Soc Lond B Biol Sci 361:1593–1610

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lööv C, Fernqvist M, Walmsley A, Marklund N, Erlandsson A (2012) Neutralization of LINGO-1 during in vitro differentiation of neural stem cells results in proliferation of immature neurons. PLoS One 7:e29771

    PubMed Central  PubMed  Google Scholar 

  • Louissaint A Jr, Rao S, Leventhal C, Goldman SA (2002) Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron 34:945–960

    CAS  PubMed  Google Scholar 

  • Lu H, Jiao Q, Wang Y, Yang Z, Feng M, Wang L, Chen X, Jin W, Liu Y (2013) The mental retardation-associated protein srGAP3 regulates survival, proliferation, and differentiation of rat embryonic neural stem/progenitor cells. Stem Cells Dev 22:1709–1716

    CAS  PubMed  Google Scholar 

  • Ma DK, Kim WR, Ming G, H. S (2009) Activity‐dependent extrinsic regulation of adult olfactory bulb and hippocampal neurogenesis. Ann N Y Acad Sci 1170:664–673

    PubMed Central  PubMed  Google Scholar 

  • Marcos S, Backer S, Causeret F, Tessier-Lavigne M, Bloch-Gallego E (2009) Differential roles of Netrin-1 and its receptor DCC in inferior olivary neuron migration. Mol Cell Neurosci 41:429–439

    CAS  PubMed  Google Scholar 

  • Marillat V, Cases O, Nguyen-Ba-Charvet KT, Tessier-Lavigne M, Sotelo C, Chedotal A (2002) Spatiotemporal expression patterns of slit and robo genes in the rat brain. J Comp Neurol 442:130–155

    PubMed  Google Scholar 

  • Martin I, Andres CR, Vedrine S, Tabagh R, Michelle C, Jourdan ML, Heuze-Vourc’h N, Corcia P, Duittoz A, Vourc’h P (2009) Effect of the oligodendrocyte myelin glycoprotein (OMgp) on the expansion and neuronal differentiation of rat neural stem cells. Brain Res 1284:22–30

    CAS  PubMed  Google Scholar 

  • Mathis C, Schröter A, Thallmair M, Schwab ME (2010) Nogo-A regulates neural precursor migration in the embryonic mouse cortex. Cereb Cortex 20:2380–2390

    PubMed Central  PubMed  Google Scholar 

  • Mehta B, Bhat KM (2001) Slit signaling promotes the terminal asymmetric division of neural precursor cells in the Drosophila CNS. Development 128:3161–3168

    CAS  PubMed  Google Scholar 

  • Merlos-Suarez A, Batlle E (2008) Eph-ephrin signalling in adult tissues and cancer. Curr Opin Cell Biol 20:194–200

    CAS  PubMed  Google Scholar 

  • Mi Y, Gao X, Ma Y, Gao J, Wang Z, JinW (2014) A novel centrosome and microtubules associated subcellular localization of Nogo-A: implications for neuronal development. Int J Biochem Cell Biol 57:1–6. doi:10.1016/j.biocel.2014.09.024

  • Ming G-l, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250

    CAS  PubMed  Google Scholar 

  • Murai K, Qiu R, Zhang H, Wang J, Wu C, Neubig RR, Lu Q (2010) Galpha subunit coordinates with ephrin-B to balance self-renewal and differentiation in neural progenitor cells. Stem Cells 28:1581–1589

    CAS  PubMed Central  PubMed  Google Scholar 

  • Murase S, Horwitz AF (2002) Deleted in colorectal carcinoma and differentially expressed integrins mediate the directional migration of neural precursors in the rostral migratory stream. J Neurosci 22:3568–3579

    CAS  PubMed  Google Scholar 

  • Niclou SP, Ehlert EM, Verhaagen J (2006) Chemorepellent axon guidance molecules in spinal cord injury. J Neurotrauma 23:409–421

    PubMed  Google Scholar 

  • North HA, Zhao X, Kolk SM, Clifford MA, Ziskind DM, Donoghue MJ (2009) Promotion of proliferation in the developing cerebral cortex by EphA4 forward signaling. Development 136:2467–2476

    CAS  PubMed Central  PubMed  Google Scholar 

  • O’Leary CJ, Bradford D, Chen M, White A, Blackmore DG, Cooper HM (2014) The Netrin/RGM receptor, neogenin, controls adult neurogenesis by promoting neuroblast migration and cell cycle exit. Stem Cells. doi:10.1002/stem.1861

    Google Scholar 

  • Ottone C, Krusche B, Whitby A, Clements M, Quadrato G, Pitulescu ME, Adams RH, Parrinello S (2014) Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells. Nat Cell Biol 16:1045–1056

    CAS  PubMed Central  PubMed  Google Scholar 

  • Park JH, Strittmatter SM (2007) Nogo receptor interacts with brain APP and Aβ to reduce pathologic changes in Alzheimer’s transgenic mice. Curr Alzheimer Res 4:568

    CAS  PubMed Central  PubMed  Google Scholar 

  • Parr A, Kulbatski I, Zahir T, Wang X, Yue C, Keating A, Tator C (2008) Transplanted adult spinal cord–derived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury. Neuroscience 155:760–770

    CAS  PubMed  Google Scholar 

  • Phillips W, Michell AW, Barker RA (2006) Neurogenesis in diseases of the central nervous system. Stem Cells Dev 15:359–379

    CAS  PubMed  Google Scholar 

  • Qiu R, Wang X, Davy A, Wu C, Murai K, Zhang H, Flanagan JG, Soriano P, Lu Q (2008) Regulation of neural progenitor cell state by ephrin-B. J Cell Biol 181:973–983

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ramasamy S, Yu F, Hong Yu Y, Srivats H, Stewart Dawe G, Ahmed S (2014) NogoR1 and PirB signaling stimulates neural stem cell survival and proliferation. Stem Cells 32:1636–1648

    CAS  PubMed  Google Scholar 

  • Ricard J, Salinas J, Garcia L, Liebl DJ (2006) EphrinB3 regulates cell proliferation and survival in adult neurogenesis. Mol Cell Neurosci 31:713–722

    CAS  PubMed  Google Scholar 

  • Riess P, Zhang C, Saatman KE, Laurer HL, Longhi LG, Raghupathi R, Lenzlinger PM, Lifshitz J, Boockvar J, Neugebauer E (2002) Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury. Neurosurgery 51:1043–1054

    PubMed  Google Scholar 

  • Robak LA, Venkatesh K, Lee H, Raiker SJ, Duan Y, Lee-Osbourne J, Hofer T, Mage RG, Rader C, Giger RJ (2009) Molecular basis of the interactions of the Nogo-66 receptor and its homolog NgR2 with myelin-associated glycoprotein: development of NgROMNI-Fc, a novel antagonist of CNS myelin inhibition. J Neurosci 29:5768–5783

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schachner M, Bartsch U (2000) Multiple functions of the myelin-associated glycoprotein MAG (siglec-4a) in formation and maintenance of myelin. GLIA 29:154–165

    CAS  PubMed  Google Scholar 

  • Schmandke A, Schmandke A, Schwab ME (2014) Nogo-A: multiple roles in CNS development, maintenance, and disease. Neurosci 20:372–386. doi:10.1177/1073858413516800

  • See J, Bonner J, Neuhuber B, Fischer I (2010) Neurite outgrowth of neural progenitors in presence of inhibitory proteoglycans. J Neurotrauma 27:951–957

    PubMed  Google Scholar 

  • Shen Y, Tenney AP, Busch SA, Horn KP, Cuascut FX, Liu K, He Z, Silver J, Flanagan JG (2009) PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 326:592–596

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sirko S, von Holst A, Wizenmann A, Gotz M, Faissner A (2007) Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells. Development 134:2727–2738

    CAS  PubMed  Google Scholar 

  • Stanco A, Szekeres C, Patel N, Rao S, Campbell K, Kreidberg JA, Polleux F, Anton ES (2009) Netrin-1-alpha3beta1 integrin interactions regulate the migration of interneurons through the cortical marginal zone. Proc Natl Acad Sci U S A 106:7595–7600

    CAS  PubMed Central  PubMed  Google Scholar 

  • Staquicini FI, Dias-Neto E, Li J, Snyder EY, Sidman RL, Pasqualini R, Arap W (2009) Discovery of a functional protein complex of netrin-4, laminin gamma1 chain, and integrin alpha6beta1 in mouse neural stem cells. Proc Natl Acad Sci U S A 106:2903–2908

    CAS  PubMed Central  PubMed  Google Scholar 

  • Suehiro K, Nakamura Y, Xu S, Uda Y, Matsumura T, Yamaguchi Y, Okamura H, Yamashita T, Takei Y (2014) Ecto-domain phosphorylation promotes functional recovery from spinal cord injury. Sci Rep 4:4972

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, Garcia-Verdugo JM, Doetsch F (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3:279–288

    CAS  PubMed  Google Scholar 

  • Tessier-Lavigne M, Goodman CS (1996) The molecular biology of axon guidance. Science 274:1123–1133

    CAS  PubMed  Google Scholar 

  • Tham M, Ramasamy S, Gan HT, Ramachandran A, Poonepalli A, Yu YH, Ahmed S (2010) CSPG is a secreted factor that stimulates neural stem cell survival possibly by enhanced EGFR signaling. PLoS One 5:e15341

    CAS  PubMed Central  PubMed  Google Scholar 

  • Theus MH, Ricard J, Bethea JR, Liebl DJ (2010) EphB3 limits the expansion of neural progenitor cells in the subventricular zone by regulating p53 during homeostasis and following traumatic brain injury. Stem Cells 28:1231–1242

    CAS  PubMed Central  PubMed  Google Scholar 

  • Uschkureit T, Spörkel O, Stracke J, Büssow H, Stoffel W (2000) Early onset of axonal degeneration in double (plp−/− mag−/−) and hypomyelinosis in triple (plp−/− mbp−/− mag−/−) mutant mice. J Neurosci 20:5225–5233

    CAS  PubMed  Google Scholar 

  • Venkatesh K, Chivatakarn O, Lee H, Joshi PS, Kantor DB, Newman BA, Mage R, Rader C, Giger RJ (2005) The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein. J Neurosci 25:808–822

    CAS  PubMed  Google Scholar 

  • Vourc’h P, Andres C (2004) Oligodendrocyte myelin glycoprotein (OMgp): evolution, structure and function. Brain Res Rev 45:115–124

    PubMed  Google Scholar 

  • Wang F, Zhu Y (2008) The interaction of Nogo-66 receptor with Nogo-p4 inhibits the neuronal differentiation of neural stem cells. Neuroscience 151:74–81

    PubMed  Google Scholar 

  • Wang B, Xiao Z, Chen B, Han J, Gao Y, Zhang J, Zhao W, Wang X, Dai J (2008) Nogo-66 promotes the differentiation of neural progenitors into astroglial lineage cells through mTOR-STAT3 pathway. PLoS One 3:e1856

    PubMed Central  PubMed  Google Scholar 

  • Weiss S, Dunne C, Hewson J, Wohl C, Wheatley M, Peterson AC, Reynolds BA (1996) Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J Neurosci 16:7599–7609

    CAS  PubMed  Google Scholar 

  • Wilkinson DG (2001) Multiple roles of EPH receptors and ephrins in neural development. Nat Rev Neurosci 2:155–164

    CAS  PubMed  Google Scholar 

  • Wu H, Fan J, Zhu L, Liu S, Wu Y, Zhao T, Ding X, Fan W, Fan M (2009) Sema4C expression in neural stem/progenitor cells and in adult neurogenesis induced by cerebral ischemia. J Mol Neurosci 39:27–39

    CAS  PubMed  Google Scholar 

  • Xing S, He Y, Ling L, Hou Q, Yu J, Zeng J, Pei Z (2008) Blockade of EphB2 enhances neurogenesis in the subventricular zone and improves neurological function after cerebral cortical infarction in hypertensive rats. Brain Res 1230:237–246

    CAS  PubMed  Google Scholar 

  • Xu L, Xu CJ, Lu HZ, Wang YX, Li Y, Lu PH (2010) Long-term fate of allogeneic neural stem cells following transplantation into injured spinal cord. Stem Cell Rev 6:121–136

    PubMed  Google Scholar 

  • Xu CJ, Xu L, Huang LD, Li Y, Yu PP, Hang Q, Xu XM, Lu PH (2011) Combined NgR vaccination and neural stem cell transplantation promote functional recovery after spinal cord injury in adult rats. Neuropathol Appl Neurobiol 37:135–155

    CAS  PubMed  Google Scholar 

  • Xu DE, Zhang WM, Yang ZZ, Zhu HM, Yan K, Li S, Bagnard D, Dawe GS, Ma QH, Xiao ZC (2014a) Amyloid precursor protein at node of Ranvier modulates nodal formation. Cell Adh Migr 8:396–403

    PubMed  Google Scholar 

  • Xu K, Wu Z, Renier N, Antipenko A, Tzvetkova-Robev D, Xu Y, Minchenko M, Nardi-Dei V, Rajashankar KR, Himanen J, Tessier-Lavigne M, Nikolov DB (2014b) Neural migration. Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism. Science 344:1275–1279

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yeh ML, Gonda Y, Mommersteeg MT, Barber M, Ypsilanti AR, Hanashima C, Parnavelas JG, Andrews WD (2014) Robo1 modulates proliferation and neurogenesis in the developing neocortex. J Neurosci 34:5717–5731

    PubMed Central  PubMed  Google Scholar 

  • Yuan T, Liao W, Feng NH, Lou YL, Niu X, Zhang AJ, Wang Y, Deng ZF (2013) Human induced pluripotent stem cell-derived neural stem cells survive, migrate, differentiate, and improve neurologic function in a rat model of middle cerebral artery occlusion. Stem Cell Res Ther 4:73

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou Y, Gunput RA, Pasterkamp RJ (2008) Semaphorin signaling: progress made and promises ahead. Trends Biochem Sci 33:161–170

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The project is supported by the Zhejiang Provincial Natural Science Foundation of China (LY13H090007) and the National Natural Science Foundation of China (No. 81272801)

Conflict of interest

We declare that we did not receive financial support or maintain relationships that may pose a conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Chao-Jin Xu or Wei-Lin Jin.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, CJ., Wang, JL. & Jin, WL. The Neural Stem Cell Microenvironment: Focusing on Axon Guidance Molecules and Myelin-Associated Factors. J Mol Neurosci 56, 887–897 (2015). https://doi.org/10.1007/s12031-015-0538-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-015-0538-1

Keywords

Navigation