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Regulation of Asymmetric Cell Division in Mammalian Neural Stem and Cancer Precursor Cells

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Asymmetric Cell Division in Development, Differentiation and Cancer

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 61))

Abstract

Stem and progenitor cells are characterized by their abilities to self-renew and produce differentiated progeny. The balance between self-renewal and differentiation is achieved through control of cell division mode, which can be either asymmetric or symmetric. Failure to properly control cell division mode may result in premature depletion of the stem/progenitor cell pool or abnormal growth and impaired differentiation. In many tissues, including the brain, stem cells and progenitor cells undergo asymmetric cell division through the establishment of cell polarity. Cell polarity proteins are therefore potentially critical regulators of asymmetric cell division. Decrease or loss of asymmetric cell division can be associated with reduced differentiation common during aging or impaired remyelination as seen in demyelinating diseases. Progenitor-like glioma precursor cells show decreased asymmetric cell division rates and increased symmetric divisions, which suggests that asymmetric cell division suppresses brain tumor formation. Cancer stem cells, on the other hand, still undergo low rates of asymmetric cell division, which may provide them with a survival advantage during therapy. These findings led to the hypotheses that asymmetric cell divisions are not always tumor suppressive but can also be utilized to maintain a cancer stem cell population. Proper control of cell division mode is therefore not only deemed necessary to generate cellular diversity during development and to maintain adult tissue homeostasis but may also prevent disease and determine disease progression. Since brain cancer is most common in the adult and aging population, we review here the current knowledge on molecular mechanisms that regulate asymmetric cell divisions in the neural and oligodendroglial lineage during development and in the adult brain.

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References

  • Ahlenius H, Visan V, Kokaia M, Lindvall O, Kokaia Z (2009) Neural stem and progenitor cells retain their potential for proliferation and differentiation into functional neurons despite lower number in aged brain. J Neurosci 29:4408–4419

    Article  CAS  PubMed  Google Scholar 

  • Alvarez-Buylla A, Garcia-Verdugo JM, Tramontin AD (2001) A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2:287–293

    Article  CAS  PubMed  Google Scholar 

  • Andreu-Agulló C, Morante-Redolat JM, Delgado AC, Fariñas I (2009) Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone. Nat Neurosci 12:1514–1523

    Article  PubMed  CAS  Google Scholar 

  • Atwood SX, Prehoda KE (2009) aPKC phosphorylates Miranda to polarize fate determinants during neuroblast asymmetric cell division. Curr Biol 19:723–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atwood SX, Chabu C, Penkert RR, Doe CQ, Prehoda KE (2007) Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6 aPKC. J Cell Sci 120:3200–3206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balordi F, Fishell G (2007a) Mosaic removal of hedgehog signaling in the adult SVZ reveals that the residual wild-type stem cells have a limited capacity for self-renewal. J Neurosci 27:14248–14259

    Article  CAS  PubMed  Google Scholar 

  • Balordi F, Fishell G (2007b) Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons. J Neurosci 27:5936–5947

    Article  CAS  PubMed  Google Scholar 

  • Betschinger J, Mechtler K, Knoblich JJA (2003) The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 422:326–330

    Article  CAS  PubMed  Google Scholar 

  • Betschinger J, Mechtler K, Knoblich JA (2006) Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell 124:1241–1253

    Article  CAS  PubMed  Google Scholar 

  • Blackmore DG, Golmohammadi MG, Large B, Waters MJ, Rietze RL (2009) Exercise increases neural stem cell number in a growth hormone-dependent manner, augmenting the regenerative response in aged mice. Stem Cells 27:2044–2052

    Article  CAS  PubMed  Google Scholar 

  • Boda E, Di Maria S, Rosa P, Taylor V, Abbracchio M, Buffo A (2015) Early phenotypic asymmetry of sister oligodendrocyte progenitor cells after mitosis and its modulation by aging and extrinsic factors. Glia 63:271–286

    Article  PubMed  Google Scholar 

  • Bonaguidi MA, Wheeler MA, Shapiro JS, Stadel RP, Sun GJ, Ming GL, Song H (2011) In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell 145:1142–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bouab M, Paliouras GN, Aumont A, Forest-Berard K, Fernandes KJL (2011) Aging of the subventricular zone neural stem cell niche: evidence for quiescence-associated changes between early and mid-adulthood. Neuroscience 173:135–149

    Article  CAS  PubMed  Google Scholar 

  • Bowman SK, Neumüller RA, Novatchkova M, Du Q, Knoblich JA (2006) The Drosophila NuMA Homolog Mud regulates spindle orientation in asymmetric cell division. Dev Cell 10:731–742

    Article  CAS  PubMed  Google Scholar 

  • Bunk EC, Ertaylan G, Ortega F, Pavlou MA, Gonzalez Cano L, Stergiopoulos A, Safaiyan S, Völs S, van Cann M, Politis PK, Simons M, Berninger B, Del Sol A, Schwamborn JC (2016) Prox1 is required for oligodendrocyte cell identity in adult neural stem cells of the subventricular zone. Stem Cells 34(8):2115–2129

    Article  CAS  PubMed  Google Scholar 

  • Calzolari F, Michel J, Baumgart EV, Theis F, Götz M, Ninkovic J, Gotz M, Ninkovic J (2015) Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone. Nat Neurosci 18:490–492

    Article  CAS  PubMed  Google Scholar 

  • Capilla-Gonzalez V, Cebrian-Silla A, Guerrero-Cazares H, Garcia-Verdugo JM, Quinones-Hinojosa A (2013) The generation of oligodendroglial cells is preserved in the rostral migratory stream during aging. Front Cell Neurosci 7:147

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Capilla-Gonzalez V, Cebrian-Silla A, Guerrero-Cazares H, Garcia-Verdugo JM, Quinones-Hinojosa A (2014) Age-related changes in astrocytic and ependymal cells of the subventricular zone. Glia 62:790–803

    Article  PubMed  PubMed Central  Google Scholar 

  • Cicalese A, Bonizzi G, Pasi CE, Faretta M, Ronzoni S, Giulini B, Brisken C, Minucci S, Di Fiore PP, Pelicci PG (2009) The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 138:1083–1095

    Article  CAS  PubMed  Google Scholar 

  • Clarke LE, Young KM, Hamilton NB, Li H, Richardson WD, Attwell D (2012) Properties and fate of oligodendrocyte progenitor cells in the corpus callosum, motor cortex, and piriform cortex of the mouse. J Neurosci 32:8173–8185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conduit PT (2013) The dominant force of Centrobin in centrosome asymmetry. Nat Cell Biol 15:235–237

    Article  CAS  PubMed  Google Scholar 

  • Costa MR, Ortega F, Brill MS, Beckervordersandforth R, Petrone C, Schroeder T, Gotz M, Berninger B (2011) Continuous live imaging of adult neural stem cell division and lineage progression in vitro. Development 138:1057–1068

    Article  CAS  PubMed  Google Scholar 

  • Daynac M, Pineda JR, Chicheportiche A, Gauthier LR, Morizur L, Boussin FD, Mouthon MA (2014) TGFbeta lengthens the G1 phase of stem cells in aged mouse brain. Stem Cells 32:3257–3265

    Article  CAS  PubMed  Google Scholar 

  • Daynac M, Morizur L, Chicheportiche A, Mouthon MA, Boussin FD (2016a) Age-related neurogenesis decline in the subventricular zone is associated with specific cell cycle regulation changes in activated neural stem cells. Sci Rep 6:21505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daynac M, Tirou L, Faure H, Mouthon MA, Gauthier LR, Hahn H, Boussin FD, Ruat M (2016b) Hedgehog controls quiescence and activation of neural stem cells in the adult ventricular-subventricular zone. Stem Cell Reports 7:735–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dimou L, Simon C, Kirchhoff F, Takebayashi H, Götz M, Gotz M (2008) Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex. J Neurosci 28:10434–10442

    Article  CAS  PubMed  Google Scholar 

  • Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17:5046–5061

    CAS  PubMed  Google Scholar 

  • Doetsch F, Caillé I, Lim DA, García-Verdugo JM, Alvarez-Buylla A, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716

    Article  CAS  PubMed  Google Scholar 

  • Du Q, Stukenberg PT, Macara IG (2001) A mammalian partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nat Cell Biol 3:1069–1075

    Article  CAS  PubMed  Google Scholar 

  • Dyer MA, Livesey FJ, Cepko CL, Oliver G (2003) Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nat Genet 34:53–58

    Article  CAS  PubMed  Google Scholar 

  • Encinas JM, Vaahtokari A, Enikolopov G (2006) Fluoxetine targets early progenitor cells in the adult brain. Proc Natl Acad Sci USA 103:8233–8238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Enwere E, Shingo T, Gregg C, Fujikawa H, Ohta S, Weiss S (2004) Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci 24:8354–8365

    Article  CAS  PubMed  Google Scholar 

  • Erben V, Waldhuber M, Langer D, Fetka I, Jansen RP, Petritsch C (2008) Asymmetric localization of the adaptor protein Miranda in neuroblasts is achieved by diffusion and sequential interaction of Myosin II and VI. J Cell Sci 121:1403–1414

    Article  CAS  PubMed  Google Scholar 

  • Eroglu E, Burkard TR, Jiang Y, Saini N, Homem CCF, Reichert H, Knoblich JA (2014) SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells. Cell 156:1259–1273

    Article  CAS  PubMed  Google Scholar 

  • Ferent J, Cochard L, Faure H, Taddei M, Hahn H, Ruat M, Traiffort E (2014) Genetic activation of Hedgehog signaling unbalances the rate of neural stem cell renewal by increasing symmetric divisions. Stem Cell Rep 3:312–323

    Article  CAS  Google Scholar 

  • Ferron SRSSR, Pozo N, Laguna A, Aranda S, Porlan E, Moreno M, Fillat C, de la Luna S, Sánchez P, Arbonés ML, Fariñas I, Sanchez P, Arbones ML, Farinas I (2010) Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling. Cell Stem Cell 7:367–379

    Article  CAS  PubMed  Google Scholar 

  • Fietz SA, Kelava I, Vogt J, Wilsch-Brauninger M, Stenzel D, Fish JL, Corbeil D, Riehn A, Distler W, Nitsch R, Huttner WB (2010) OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat Neurosci 13:690–699

    Article  CAS  PubMed  Google Scholar 

  • Florio M, Huttner WB (2014) Neural progenitors, neurogenesis and the evolution of the neocortex. Development 141:2182–2194

    Article  CAS  PubMed  Google Scholar 

  • Fuentealba LC, Rompani SB, Parraguez JI, Obernier K, Romero R, Cepko CL, Alvarez-Buylla A (2015) Embryonic origin of postnatal neural stem cells. Cell 161:1644–1655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furutachi S, Matsumoto A, Nakayama KI, Gotoh Y (2013) p57 controls adult neural stem cell quiescence and modulates the pace of lifelong neurogenesis. EMBO J 32:970–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furutachi S, Miya H, Watanabe T, Kawai H, Yamasaki N, Harada Y, Imayoshi I, Nelson M, Nakayama KI, Hirabayashi Y, Gotoh Y (2015) Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells. Nat Neurosci 18:657–665

    Article  CAS  PubMed  Google Scholar 

  • Gage FH, Kempermann G, Palmer TD, Peterson DA, Ray J (1998) Multipotent progenitor cells in the adult dentate gyrus. J Neurobiol 36:249–266

    Article  CAS  PubMed  Google Scholar 

  • Gallo V, Deneen B (2014) Glial development: the crossroads of regeneration and repair in the CNS. Neuron 83(2):283–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao P, Postiglione MP, Krieger TG, Hernandez L, Wang C, Han Z, Streicher C, Papusheva E, Insolera R, Chugh K, Kodish O, Huang K, Simons BD, Luo L, Hippenmeyer S, Shi SH (2014) Deterministic progenitor behavior and unitary production of neurons in the neocortex. Cell 159:775–788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomez-Lopez S, Lerner RG, Petritsch C, Gómez-López S, Lerner RG, Petritsch C (2013) Asymmetric cell division of stem and progenitor cells during homeostasis and cancer. CMLS 71:575–597

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gonzalez-Perez O, Romero-Rodriguez R, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A (2009) Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes. Stem Cells 27:2032–2043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gotz M, Huttner WB (2005) The cell biology of neurogenesis. Nat Rev Mol Cell Biol 6:777–788

    Article  PubMed  CAS  Google Scholar 

  • Greig LC, Woodworth MB, Galazo MJ, Padmanabhan H, Macklis JD (2013) Molecular logic of neocortical projection neuron specification, development and diversity. Nat Rev Neurosci 14:755–769

    Article  CAS  PubMed  Google Scholar 

  • Hansen DV, Lui JH, Parker PRL, Kriegstein AR (2010) Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464:554–561

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hill R, Patel K, Goncalves C, Grutzendler J, Nishiyama A (2014) Modulation of oligodendrocyte generation during a critical temporal window after NG2 cell division. Nat Neurosci 17:1518–1527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes EG, Kang SH, Fukaya M, Bergles DE (2013) Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nat Neurosci 16:668–676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ikeshima-Kataoka H, Skeath JB, Nabeshima Y, Doe CQ, Matsuzaki F (1997) Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions. Nature 390:625–629

    Article  CAS  PubMed  Google Scholar 

  • Izumi Y, Ohta N, Hisata K, Raabe T, Matsuzaki F (2006) Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization. Nat Cell Biol 8:586–593

    Article  CAS  PubMed  Google Scholar 

  • Januschke J, Llamazares S, Reina J, Gonzalez C (2011) Drosophila neuroblasts retain the daughter centrosome. Nat Commun 2:243

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Januschke J, Reina J, Llamazares S, Bertran T, Rossi F, Roig J, Gonzalez C (2013) Centrobin controls mother-daughter centriole asymmetry in Drosophila neuroblasts. Nat Cell Biol 15:241–248

    Article  CAS  PubMed  Google Scholar 

  • Kang S, Fukaya M, Yang J, Rothstein J, Bergles D (2010) NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. Neuron 68:668–681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197(4308):1092–1094

    Article  CAS  PubMed  Google Scholar 

  • Kato K, Konno D, Berry M, Matsuzaki F, Logan A, Hidalgo A (2015) Prox1 inhibits proliferation and is required for differentiation of the oligodendrocyte cell lineage in the mouse. PLoS One 10:1–19

    Google Scholar 

  • Kawaguchi D, Furutachi S, Kawai H, Hozumi K, Gotoh Y (2013) Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis. Nat Commun 4:1880

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495

    Article  CAS  PubMed  Google Scholar 

  • Kessaris N, Fogarty M, Iannarelli P, Grist M, Wegner M, Richardson WD (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci 9:173–179

    Article  CAS  PubMed  Google Scholar 

  • Knoth R, Singec I, Ditter M, Pantazis G, Capetian P, Meyer RP, Horvat V, Volk B, Kempermann G (2010) Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS One 5

    Google Scholar 

  • Konno D, Shioi G, Shitamukai A, Mori A, Kiyonari H, Miyata T, Matsuzaki F (2008) Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat Cell Biol 10:93–101

    Article  CAS  PubMed  Google Scholar 

  • Kuo CT, Mirzadeh Z, Soriano-Navarro M, Rasin M, Wang D, Shen J, Sestan N, Garcia-Verdugo J, Alvarez-Buylla A, Jan LY, Jan Y-NN (2006) Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. Cell 127:1253–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kusek G, Campbell M, Doyle F, Tenenbaum SA, Kiebler M, Temple S (2012) Asymmetric segregation of the double-stranded RNA binding protein Staufen2 during mammalian neural stem cell divisions promotes lineage progression. Cell Stem Cell 11:505–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee C-YY, Andersen RO, Cabernard C, Manning L, Tran KD, Lanskey MJ, Bashirullah A, Doe CQ (2006a) Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev 20:3464–3474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee C-YY, Wilkinson BD, Siegrist SE, Wharton RP, Doe CQ (2006b) Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell 10:441–449

    Article  CAS  PubMed  Google Scholar 

  • Lerner RG, Grossauer S, Kadkhodaei B, Meyers I, Sidorov M, Koeck K, Hashizume R, Ozawa T, Phillips JJ, Berger MS, Nicolaides T, James CD, Petritsch CK (2015) Targeting a Plk1-controlled polarity checkpoint in therapy-resistant glioblastoma-propagating cells. Cancer Res 75:5355–5366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li G, Fang L, Fernandez G, Pleasure S (2013) The ventral hippocampus is the embryonic origin for adult neural stem cells in the dentate gyrus. Neuron 78:658–672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu H, Song N (2016) Molecular mechanism of adult neurogenesis and its association with human brain diseases. J Cent Nerv Syst Dis 8:5–11

    Article  PubMed  PubMed Central  Google Scholar 

  • Lois C, Alvarez-Buylla A (1993) Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci USA 90:2074–2077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu B, Rothenberg M, Jan LY, Jan YN (1998) Partner of Numb colocalizes with Numb during mitosis and directs Numb asymmetric localization in Drosophila neural and muscle progenitors. Cell 95:225–235

    Article  CAS  PubMed  Google Scholar 

  • Lu QR, Yuk D, Alberta JA, Zhu Z, Pawlitzky I, Chan J, McMahon AP, Stiles CD, Rowitch DH (2000) Sonic hedgehog–regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron 25:317–329

    Article  CAS  PubMed  Google Scholar 

  • Lugert S, Basak O, Knuckles P, Haussler U, Fabel K, Gotz M, Haas CA, Kempermann G, Taylor V, Giachino C, Götz M, Haas CA, Kempermann G, Taylor V, Giachino C, Gotz M, Haas CA, Kempermann G, Taylor V, Giachino C (2010) Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell 6:445–456

    Article  CAS  PubMed  Google Scholar 

  • Luskin MB (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11:173–189

    Article  CAS  PubMed  Google Scholar 

  • Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110

    CAS  PubMed  Google Scholar 

  • Marques S, Zeisel A, Codeluppi S, van Bruggen D, Mendanha Falcão A, Xiao L, Li H, Häring M, Hochgerner H, Romanov RA, Gyllborg D, Muñoz-Manchado AB, La Manno G, Lönnerberg P, Floriddia EM, Rezayee F, Ernfors P, Arenas E, Hjerling-Leffler J, Harkany T, Richardson WD, Linnarsson S, Castelo-Branco G (2016) Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system. Science 352:1326–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maslov AY, Barone TA, Plunkett RJ, Pruitt SC (2004) Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice. J Neurosci 24:1726–1733

    Article  CAS  PubMed  Google Scholar 

  • Matsuzaki F, Ohshiro T, Ikeshima-Kataoka H, Izumi H (1998) miranda localizes staufen and prospero asymmetrically in mitotic neuroblasts and epithelial cells in early Drosophila embryogenesis. Development 125:4089–4098

    CAS  PubMed  Google Scholar 

  • Menn B, Garcia-Verdugo JM, Yaschine C, Gonzalez-Perez O, Rowitch D, Alvarez-Buylla A (2006) Origin of oligodendrocytes in the subventricular zone of the adult brain. J Neurosci 26:7907–7918

    Article  CAS  PubMed  Google Scholar 

  • Mignone JL, Kukekov V, Chiang A-S, Steindler D, Enikolopov G (2004) Neural stem and progenitor cells in nestin-GFP transgenic mice. J Comp Neurol 469:311–324

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A (2008) Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3:265–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neumüller RA, Richter C, Fischer A, Novatchkova M, Neumüller KG, Knoblich JA (2011) Genome-wide analysis of self-renewal in Drosophila neural stem cells by transgenic RNAi. Cell Stem Cell 8:580–593

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR, Martínez-Cerdeño V, Ivic L, Kriegstein AR, Martinez-Cerdeno V, Ivic L, Kriegstein AR (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7:136–144

    Article  CAS  PubMed  Google Scholar 

  • Noctor SC, Martinez-Cerdeno V, Kriegstein AR, Martínez-Cerdeño V, Kriegstein AR, Martinez-Cerdeno V, Kriegstein AR (2008) Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J Comp Neurol 508:28–44

    Article  PubMed  PubMed Central  Google Scholar 

  • Ogawa H, Ohta N, Moon W, Matsuzaki F (2009) Protein phosphatase 2A negatively regulates aPKC signaling by modulating phosphorylation of Par-6 in Drosophila neuroblast asymmetric divisions. J Cell Sci 122:3242–3249

    Article  CAS  PubMed  Google Scholar 

  • Orentas DM, Hayes JE, Dyer KL, Miller RH (1999) Sonic hedgehog signaling is required during the appearance of spinal cord oligodendrocyte precursors. Development 126:2419–2429

    CAS  PubMed  Google Scholar 

  • Ortega F, Gascon S, Masserdotti G, Deshpande A, Simon C, Fischer J, Dimou L, Chichung Lie D, Schroeder T, Berninger B, Gascón S, Masserdotti G, Deshpande A, Simon C, Fischer J, Dimou L, Chichung Lie D, Schroeder T, Berninger B, Gascon S, Masserdotti G, Deshpande A, Simon C, Fischer J, Dimou L, Chichung Lie D, Schroeder T, Berninger B (2013) Oligodendrogliogenic and neurogenic adult subependymal zone neural stem cells constitute distinct lineages and exhibit differential responsiveness to Wnt signalling. Nat Cell Biol 15:602–613

    Article  CAS  PubMed  Google Scholar 

  • Petersen PH, Zou K, Hwang JK, Jan YN, Zhong W (2002) Progenitor cell maintenance requires numb and numblike during mouse neurogenesis. Nature 419:929–934

    Article  CAS  PubMed  Google Scholar 

  • Peterson FC, Penkert RR, Volkman BF, Prehoda KE (2004) Cdc42 regulates the Par-6 PDZ domain through an allosteric CRIB-PDZ transition. Mol Cell 13:665–676

    Article  CAS  PubMed  Google Scholar 

  • Petritsch C, Tavosanis G, Turck CW, Jan LY, Jan YN (2003) The Drosophila myosin VI Jaguar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts. Dev Cell 4:273–281

    Article  CAS  PubMed  Google Scholar 

  • Piccin D, Tufford A, Morshead CM (2014) Neural stem and progenitor cells in the aged subependyma are activated by the young niche. Neurobiol Aging 35:1669–1679

    Article  PubMed  Google Scholar 

  • Pineda JR, Daynac M, Chicheportiche A, Cebrian-Silla A, Sii Felice K, Garcia-Verdugo JM, Boussin FD, Mouthon MA (2013) Vascular-derived TGF-beta increases in the stem cell niche and perturbs neurogenesis during aging and following irradiation in the adult mouse brain. EMBO Mol Med 5:548–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ponti G, Obernier K, Guinto C, Jose L, Bonfanti L, Alvarez-Buylla A (2013) Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice. Proc Natl Acad Sci USA 110:E1045–E1054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Postiglione MP, Jüschke C, Xie Y, Haas GA, Charalambous C, Knoblich JA (2011) Mouse inscuteable induces apical-basal spindle orientation to facilitate intermediate progenitor generation in the developing neocortex. Neuron 72:269–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Psachoulia K, Jamen F, Young KM, Richardson WD (2009) Cell cycle dynamics of NG2 cells in the postnatal and ageing brain. Neuron Glia Biol 5:57–67

    Article  PubMed  Google Scholar 

  • Rakic P (1995) A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci 18:383–388

    Article  CAS  PubMed  Google Scholar 

  • Rebollo E, Sampaio P, Januscke J, Llamazares S, Varmerk H, Gonzalez C, Januschke J, Llamazares S, Varmark H, González C (2007) Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. Dev Cell 12:467–474

    Article  CAS  PubMed  Google Scholar 

  • Rivers LE, Young KM, Rizzi M, Jamen F, Psachoulia K, Wade A, Kessaris N, Richardson WD (2008) PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci 11:1392–1401

    Article  CAS  PubMed  Google Scholar 

  • Rolls MM, Albertson R, Shih H-PP, Lee C-YY, Doe CQ (2003) Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J Cell Biol 163:1089–1098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rowitch DH, Kriegstein AR (2010) Developmental genetics of vertebrate glial-cell specification. Nature 468:214–222

    Article  CAS  PubMed  Google Scholar 

  • Sakai D, Dixon J, Dixon MJ, Trainor PA (2012) Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle orientation, mitotic progression, and maintenance of neural progenitor cells. PLoS Genet 8:e1002566

    Article  PubMed  PubMed Central  Google Scholar 

  • Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai H-H, Wong M, Gupta N, Berger MS, Huang E, Garcia-Verdugo J-MM, Rowitch DH, Alvarez-Buylla A (2011) Corridors of migrating neurons in the human brain and their decline during infancy. Nature 478:382–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaefer M, Shevchenko A, Knoblich JA (2000) A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Curr Biol 10:353–362

    Article  CAS  PubMed  Google Scholar 

  • Schwamborn JC, Berezikov E, Knoblich JA (2009) The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 136:913–925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen CP, Jan LY, Jan YN (1997) Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila. Cell 90:449–458

    Article  CAS  PubMed  Google Scholar 

  • Shen CP, Knoblich JA, Chan YM, Jiang MM, Jan LY, Jan YN (1998) Miranda as a multidomain adapter linking apically localized Inscuteable and basally localized Staufen and Prospero during asymmetric cell division in Drosophila. Genes Dev 12:1837–1846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen Q, Zhong W, Jan YN, Temple S (2002) Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts. Development 129:4843–4853

    CAS  PubMed  Google Scholar 

  • Shen Q, Wang Y, Kokovay E, Lin G, Chuang S-MM, Goderie SK, Roysam B, Temple S (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 3:289–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shitamukai A, Konno D, Matsuzaki F (2011) Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors. J Neurosci 31:3683–3695

    Article  CAS  PubMed  Google Scholar 

  • Shook BA, Manz DH, Peters JJ, Kang S, Conover JC (2012) Spatiotemporal changes to the subventricular zone stem cell pool through aging. J Neurosci 32:6947–6956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegrist SE, Doe CQ (2005) Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell 123:1323–1335

    Article  CAS  PubMed  Google Scholar 

  • Siegrist SE, Doe CQ (2007) Microtubule-induced cortical cell polarity. Genes Dev 21:483–496

    Article  CAS  PubMed  Google Scholar 

  • Siller KH, Doe CQ (2009) Spindle orientation during asymmetric cell division. Nat Cell Biol 11:365–374

    Article  CAS  PubMed  Google Scholar 

  • Siller KH, Cabernard C, Doe CQ (2006) The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts. Nat Biotechnol 8:594–600

    CAS  Google Scholar 

  • Sim FJ, Zhao C, Penderis J, Franklin RJM (2002) The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci 22:2451–2459

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Singh P, Ramdas Nair A, Cabernard C (2014) The centriolar protein Bld10/Cep135 is required to establish centrosome asymmetry in Drosophila neuroblasts. Curr Biol 24:1548–1555

    Article  CAS  PubMed  Google Scholar 

  • Slack C, Overton PM, Tuxworth RI, Chia W (2007) Asymmetric localisation of Miranda and its cargo proteins during neuroblast division requires the anaphase-promoting complex/cyclosome. Development 134:3781–3787

    Article  CAS  PubMed  Google Scholar 

  • Smith CA, Lau KM, Rahmani Z, Dho SE, Brothers G, She YM, Berry DM, Bonneil E, Thibault P, Schweisguth F, Le Borgne R, McGlade CJ (2007) aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. EMBO J 26:468–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, Boström E, Westerlund I, Vial C, Buchholz BA, Possnert G, Mash DC, Druid H, Frisén J (2013) Dynamics of hippocampal neurogenesis in adult humans. Cell 153:1219–1227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spassky N, Merkle FT, Flames N, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A, García-Verdugo JM, Alvarez-Buylla A, Garcia-Verdugo JM, Alvarez-Buylla A (2005) Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci 25:10–18

    Article  CAS  PubMed  Google Scholar 

  • Stein-Behrens B, Mattson MP, Chang I, Yeh M, Sapolsky R (1994) Stress exacerbates neuron loss and cytoskeletal pathology in the hippocampus. J Neurosci 14:5373–5380

    CAS  PubMed  Google Scholar 

  • Sugiarto S, Persson A, Munoz E, Waldhuber M, Lamagna C, Andor N, Hanecker P, Ayers-Ringler J, Phillips J, Siu J, Lim D, Vandenberg S, Stallcup W, Berger M, Bergers G, Weiss W, Petritsch C (2011) Asymmetry-defective oligodendrocyte progenitors are glioma precursors. Cancer Cell 20:328–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun Y, Goderie S, Temple S (2005) Asymmetric distribution of EGFR receptor during mitosis generates diverse CNS progenitor cells. Neuron 45:873–886. doi:10.1016/j.neuron.2005.01.045

    Article  CAS  PubMed  Google Scholar 

  • Tropepe V, Craig CG, Morshead CM, VanderKooy D (1997) Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J Neurosci 17:7850–7859

    CAS  PubMed  Google Scholar 

  • Vallstedt A, Klos JM, Ericson J (2005) Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron 45:55–67

    Article  CAS  PubMed  Google Scholar 

  • van Wijngaarden P, Franklin RJ (2013) Ageing stem and progenitor cells: implications for rejuvenation of the central nervous system. Development 140:2562–2575

    Article  PubMed  CAS  Google Scholar 

  • Vessey JP, Amadei G, Burns SE, Kiebler MA, Kaplan DR, Miller FD (2012) An asymmetrically localized staufen2-dependent RNA complex regulates maintenance of Mammalian neural stem cells. Cell Stem Cell 11:517–528

    Article  CAS  PubMed  Google Scholar 

  • Voigt T (1989) Development of glial cells in the cerebral wall of ferrets: direct tracing of their transformation from radial glia into astrocytes. J Comp Neurol 289:74–88

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Somers GW, Bashirullah A, Heberlein U, Yu F, Chia W (2006) Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Genes Dev 20:3453–3463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Ouyang Y, Somers WG, Chia W, Lu B (2007) Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon. Nature 449:96–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Tsai J-W, Imai JH, Lian W-N, Vallee RB, Shi S-H (2009) Asymmetric centrosome inheritance maintains neural progenitors in the neocortex. Nature 461:947–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang C, Liu F, Liu Y-Y, Zhao C-H, You Y, Wang L, Zhang J, Wei B, Ma T, Zhang Q, Zhang Y, Chen R, Song H, Yang Z (2011a) Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain. Cell Res 21:1534–1550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Lui J, Kriegstein A (2011a) Orienting fate: spatial regulation of neurogenic division. Neuron:191–193

    Google Scholar 

  • Wang X, Tsai J, LaMonica B, Kriegstein A (2011b) A new subtype of progenitor cell in the mouse embryonic neocortex. Nat Neurosci 14:555–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willard FS, Kimple RJ, Siderovski DP (2004) Return of the GDI: the GoLoco motif in cell Division. Annu Rev Biochem 73:925–951

    Article  CAS  PubMed  Google Scholar 

  • Wirtz-Peitz F, Nishimura T, Knoblich JA (2008) Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization. Cell 135:161–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wodarz A, Ramrath A, Kuchinke U, Knust E (1999) Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts. Nature 402:544–547

    Article  CAS  PubMed  Google Scholar 

  • Wodarz A, Ramrath A, Grimm A, Knust E (2000) Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J Cell Biol 150:1361–1374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wren D, Wolswijk G, Noble M (1992) In vitro analysis of the origin and maintenance of O-2Aadult progenitor cells. J Cell Biol 116:167–176

    Article  CAS  PubMed  Google Scholar 

  • Wu M, Kwon HY, Rattis F, Blum J, Zhao C, Ashkenazi R, Jackson TL, Gaiano N, Oliver T, Reya T (2007) Imaging hematopoietic precursor division in real time. Cell Stem Cell 1:541–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young KM, Psachoulia K, Tripathi RB, Dunn SJ, Cossell L, Attwell D, Tohyama K, Richardson WD (2013) Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling. Neuron 77:873–885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu F, Wang H, Qian H, Kaushik R, Bownes M, Yang X, Chia W (2005) Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions. Genes Dev 19:1341–1353. doi:10.1101/gad.1295505.eration

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhong W, Feder JN, Jiang MM, Jan LY, Jan YN (1996) Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis. Neuron 17:43–53

    Article  CAS  PubMed  Google Scholar 

  • Zhong W, Jiang MM, Schonemann MD, Meneses JJ, Pedersen RA, Jan LY, Jan YN (2000) Mouse numb is an essential gene involved in cortical neurogenesis. Proc Natl Acad Sci USA 97:6844–6849

    Article  CAS  PubMed  PubMed Central  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 138:745–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zong H, Parada LF, Baker SJ (2015) Cell of origin for malignant gliomas and its implication in therapeutic development. Cold Spring Harb Perspect Biol 7

    Google Scholar 

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Authors and Affiliations

  1. Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, CA, USA

    Mathieu Daynac & Claudia K. Petritsch

  2. Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA

    Claudia K. Petritsch

  3. Helen Diller Comprehensive Cancer Research Center, University of California, San Francisco, CA, USA

    Claudia K. Petritsch

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  1. Mathieu Daynac
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Correspondence to Claudia K. Petritsch .

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  1. IGDR, UMR 6290, CNRS, Université de Rennes 1, Rennes, France

    Jean-Pierre Tassan

  2. Inst of Genetics & Dev of Rennes IG, CNRS/Unive Rennes 1 UMR 6290, Rennes Cedex, France

    Jacek Z. Kubiak

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Daynac, M., Petritsch, C.K. (2017). Regulation of Asymmetric Cell Division in Mammalian Neural Stem and Cancer Precursor Cells. In: Tassan, JP., Kubiak, J. (eds) Asymmetric Cell Division in Development, Differentiation and Cancer. Results and Problems in Cell Differentiation, vol 61. Springer, Cham. https://doi.org/10.1007/978-3-319-53150-2_17

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