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Cell Cycle in Development pp 529–546Cite as

Drosophila Neural Stem Cells: Cell Cycle Control of Self-Renewal, Differentiation, and Termination in Brain Development

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

Abstract

The wealth of neurons that make up the brain are generated through the proliferative activity of neural stem cells during development. This neurogenesis activity involves complex cell cycle control of proliferative self-renewal, differentiation, and termination processes in these cells. Considerable progress has been made in understanding these processes in the neural stem cell-like neuroblasts which generate the brain in the genetic model system Drosophila. Neuroblasts in the developing fly brain generate neurons through repeated series of asymmetrical cell divisions, which balance self-renewal of the neuroblast with generation of differentiated progeny through the segregation of cell fate determinants such as Numb, Prospero, and Brat to the neural progeny. A number of classical cell cycle regulators such as cdc2/CDK1, Polo, Aurora A, and cyclin E are implicated in the control of asymmetric divisions in neuroblasts linking the cell cycle to the asymmetrical division machinery. The cellular and molecular identity of the postmitotic neurons produced by proliferating neuroblasts is influenced by the timing of their exit from the cell cycle through the action of a temporal expression series of transcription factors, which include Hunchback, Kruppel, Pdm, and Castor. This temporal series is also implicated in the control of termination of neuroblast proliferation which is effected by two different cell cycle exit strategies, terminal differentiative division or programmed cell death of the neuroblast. Defects in the asymmetric division machinery which interfere with the termination of proliferation can result in uncontrolled tumorigenic overgrowth. These findings in Drosophila brain development are likely to have general relevance in neural stem cell biology and may apply to cell cycle control in mammalian brain development as well.

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References

  • Almeida MS, Bray SJ (2005) Regulation of postembryonic neuroblasts by Drosophila grainyhead. Mech Dev 122:1282–1293

    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

    CAS  PubMed  Google Scholar 

  • Arama E, Dickman D, Kimchie Z, Shearn A, Lev Z (2000) Mutations in the beta-propeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain. Oncogene 19:3706–3716

    CAS  PubMed  Google Scholar 

  • Artavanis-Tsakonas S, Simpson P (1991) Choosing a cell fate: a view from the Notch locus. Trends Genet 7:403–408

    CAS  PubMed  Google Scholar 

  • Bello BC, Hirth F, Gould AP (2003) A pulse of the Drosophila Hox protein abdominal-A schedules the end of neural proliferation via neuroblast apoptosis. Neuron 37:209–219

    CAS  PubMed  Google Scholar 

  • Bello B, Reichert H, Hirth F (2006) The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila. Development 133:2639–2648

    CAS  PubMed  Google Scholar 

  • Bello B, Holbro N, Reichert H (2007) Polycomb group genes are required for neural stem cell survival in postembryonic neurogenesis of Drosophila. Development 134:1091–1099

    CAS  PubMed  Google Scholar 

  • Bello B, Izergina N, Caussinus E, Reichert H (2008) Amplification of neural stem cell proliferation by intermediated progenitor cells in Drosophila brain development. Neural Dev 3:5

    PubMed Central  PubMed  Google Scholar 

  • Berger C, Pallavi SK, Prasad M, Shashidhara LS, Technau GM (2005) A critical role for cyclin E in cell fate determination in the central nervous system of Drosophila melanogaster. Nat Cell Biol 7:56–62

    CAS  PubMed  Google Scholar 

  • Berger C, Kannan R, Myneni S, Renner S, Shashidhara LS, Technau GM (2010) Cell cycle independent role of Cyclin E during neural fate specification in Drosophila is mediated by its regulation of Prospero function. Dev Biol 337:415–424

    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

    CAS  PubMed  Google Scholar 

  • Bhat KM, Apsel N (2004) Upregulation of Mitimere and Nubbin acts through cyclin E to confer self-renewing asymmetric division potential to neural precursor cells in Drosophila. Development 131:1123–1134

    CAS  PubMed  Google Scholar 

  • Blaschke AJ, Weiner JA, Chun J (1998) Programmed cell death is a universal feature of embryonic and postnatal neuroproliferative regions throughout the central nervous system. J Comp Neurol 396:39–50

    CAS  PubMed  Google Scholar 

  • Boone JQ, Doe CQ (2008) Identification of Drosophila type II neuroblast lineages containing transit amplifying ganglion mother cells. Dev Neurobiol 68:1185–1195

    PubMed Central  PubMed  Google Scholar 

  • Bowman SK, Neumuller 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

    CAS  PubMed  Google Scholar 

  • Bowman SK, Rolland V, Betschinger J, Kinesey KA, Emery G, Knoblich JA (2008) The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev Cell 14:535–546

    CAS  PubMed Central  PubMed  Google Scholar 

  • Britton JS, Edgar BA (1998) Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms. Development 125:2149–2158

    CAS  PubMed  Google Scholar 

  • Brody T, Odenwald WF (2000) Programmed transformations in neuroblast gene expression during Drosophila CNS lineage development. Dev Biol 226:34–44

    CAS  PubMed  Google Scholar 

  • Budirahardja Y, Gonczy P (2009) Coupling the cell cycle to development. Development 136:2861–2872

    CAS  PubMed  Google Scholar 

  • Bultje RS, Castaneda-Castellanos DR, Jan LY, Jan YN, Kriegstein A, Shi SH (2009) Mammalian Par regulates progenitor cell asymmetric division via Notch signaling in the developing neocortex. Neuron 63:189–202

    CAS  PubMed Central  PubMed  Google Scholar 

  • Campos-Ortega J, Hartenstein V (1997) The embryonic development of Drosophila melanogaster. Springer, Berlin

    Google Scholar 

  • Castellanos E, Dominguez P, Gonzalez C (2008) Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr Biol 18:1209–1214

    CAS  PubMed  Google Scholar 

  • Caussinus E, Gonzalez C (2005) Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet 37:1125–1129

    CAS  PubMed  Google Scholar 

  • Cenci C, Gould AP (2005) Drosophila grainyhead specifies late programmes of neural proliferation by regulating the mitotic activity and Hox-dependent apoptosis of neuroblasts. Development 132:3835–3845

    CAS  PubMed  Google Scholar 

  • Ceron J, Gonzalez C, Tejedor FJ (2001) Patterns of cell division and expression of asymmetric cell fate determinants in postembryonic neuroblast lineages of Drosophila. Dev Biol 230:125–138

    CAS  PubMed  Google Scholar 

  • Chia W, Somers WG, Wang H (2008) Drosophila neuroblast asymmetric divisions: cell cycle regulators, asymmetric protein localization and tumorigenesis. J Cell Biol 180:267–272

    CAS  PubMed  Google Scholar 

  • Choksi SP, Southall T, Bossing T, Edoff K, de Wit E, van Steensel B, Micklem G, Brand AH (2006) Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Dev Cell 11:775–789

    CAS  PubMed  Google Scholar 

  • Cleary MD, Doe CQ (2006) Regulation of neuroblast competence: multiple temporal identity factors specify distinct neuronal fates within a single early competence window. Genes Dev 20:429–434

    CAS  PubMed  Google Scholar 

  • Das A, Reichert H, Rodrigues V (2010) Notch regulates the generation of diverse cell types from the lateral lineage of Drosophila antennal lobe. J Neurogenet 24:42–53

    PubMed  Google Scholar 

  • Datta S (1995) Control of proliferation activation in quiescent neuroblasts of the Drosophila central nervous system. Development 121:1173–1182

    CAS  PubMed  Google Scholar 

  • Dirks P (2008) Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells. Philos Trans R Soc Lond B Biol Sci 363:139–152

    CAS  PubMed  Google Scholar 

  • Doe CQ (1992) Molecular markers for identified neuroblasts and ganglion mother cells in the Drosophila central nervous system. Development 116:855–863

    CAS  PubMed  Google Scholar 

  • Doe CQ (2008) Neural stem cells: balancing self-renewal with differentiation. Development 135:1575–1587

    CAS  PubMed  Google Scholar 

  • Doe CQ, Chu-LaGraff Q, Wright DM, Scott MP (1991) The prospero gene specifies cell fates in the Drosophila central nervous system. Cell 65:451–464

    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

    CAS  PubMed  Google Scholar 

  • Ebens AJ, Garren H, Cheyette BN, Zipursky SL (1993) The Drosophila anachronism locus: a glycoprotein secreted by glia inhibits neuroblast proliferation. Cell 74:15–27

    CAS  PubMed  Google Scholar 

  • Egger B, Boone JQ, Stevens NR, Brand AH, Doe CQ (2007) Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe. Neural Dev 2:1

    PubMed Central  PubMed  Google Scholar 

  • Egger B, Chell JM, Brand A (2008) Insights into neural stem cell biology in flies. Phil Trans R Soc B 363:39–56

    CAS  PubMed  Google Scholar 

  • Frank DJ, Edgar BA, Roth MB (2002) The Drosophila melanogaster gene brain tumor negatively regulates cell growth and ribosomal RNA synthesis. Development 129:399–407

    CAS  PubMed  Google Scholar 

  • Gonzalez C (2007) Spindle orientation, asymmetric division and tumour suppression in Drosophila stem cells. Nat Rev Genet 8:462–472

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Green P, Hartenstein AY, Hartenstein V (1993) The embryonic development of the Drosophila visual system. Cell Tissue Res 273:583–598

    CAS  PubMed  Google Scholar 

  • Grosskortenhaus R, Pearson BJ, Marusich A, Doe CQ (2005) Regulation of temporal identity transitions in Drosophila neuroblasts. Dev Cell 8:193–202

    CAS  PubMed  Google Scholar 

  • Grosskortenhaus R, Robinson KJ, Doe CQ (2006) Pdm and Castor specify late-born motor neuron identity in the NB7-1 lineage. Genes Dev 20:2618–2627

    CAS  PubMed  Google Scholar 

  • Hartenstein V, Spindler S, Pereanu W, Fung S (2008) The development of the Drosophila larval brain. In: Technau G (ed) Brain development in Drosophila melanogaster. Landes Bioscience, Austin, pp 1–31

    Google Scholar 

  • Hirata J, Nakagoshi H, Nabeshima Y, Matsuzaki F (1995) Asymmetric segregation of the homeodomain protein Prospero during Drosophila development. Nature 377:627–630

    CAS  PubMed  Google Scholar 

  • Hofbauer A, Campos-Ortega JA (1990) Proliferation pattern and early differentiation of the optic lobes in Drosophila melanogaster. Roux’s Arch Dev Biol 198:264–274

    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

    CAS  PubMed  Google Scholar 

  • Isshiki T, Pearson B, Holbrook S, Doe CQ (2001) Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny. Cell 106:511–521

    CAS  PubMed  Google Scholar 

  • Ito K, Hotta Y (1992) Proliferation pattern of postembryonic neuroblasts in the brain of Drosophila melanogaster. Dev Biol 149:134–148

    CAS  PubMed  Google Scholar 

  • Ito K, Awano W, Suzuki K, Hiromi Y, Yamamoto D (1997) The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. Development 124:761–771

    CAS  PubMed  Google Scholar 

  • Izergina N, Balmer J, Bello B, Reichert H (2009) Postembryonic development of transit amplifying neuroblast lineages in the Drosophila brain. Neural Dev 4:44

    PubMed Central  PubMed  Google Scholar 

  • Izumi Y, Ohta N, Itoh-Furuya A, Fuse N, Matsuzaki F (2004) Differential functions of G protein and Baz-aPKC signaling pathways in Drosophila neuroblast asymmetric division. J Cell Biol 164:729–738

    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

    CAS  PubMed  Google Scholar 

  • Jacob J, Maurange C, Gould AP (2008) Temporal control of neuronal diversity: common regulatory principles in insects and vertebrates? Development 135:3481–3489

    CAS  PubMed  Google Scholar 

  • Januschke J, Gonzalez C (2008) Drosophila asymmetric division, polarity and cancer. Oncogene 27:6994–7002

    CAS  PubMed  Google Scholar 

  • Kambadur R, Koizumi K, Stivers C, Nagle J, Poole SJ, Odenwald WF (1998) Regulation of POU genes by castor and hunchback establishes layered compartments in the Drosophila CNS. Genes Dev 12:246–260

    CAS  PubMed  Google Scholar 

  • Kanai MI, Okabe M, Hiromi Y (2005) seven-up Controls switching of transcription factors that specify temporal identities of Drosophila neuroblasts. Dev Cell 8:203–213

    CAS  PubMed  Google Scholar 

  • Kao CF, Lee T (2009) Birth time/order-dependent neuron type specification. Curr Opin Neurobiol 20:14–21

    PubMed Central  PubMed  Google Scholar 

  • Knoblich JA (2008) Mechanisms of asymmetric stem cell division. Cell 132:583–597

    CAS  PubMed  Google Scholar 

  • Knoblich JA, Jan LY, Jan YN (1995) Asymmetric segregation of Numb and Prospero during cell division. Nature 377:624–627

    CAS  PubMed  Google Scholar 

  • Kriegstein A, Alvarez-Bullya (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32:149–184

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kuchinke U, Grawe F, Knust E (1998) Control of spindle orientation in Drosophila by the Par-3-related PDZdomain protein Bazooka. Curr Biol 8:1357–1365

    CAS  PubMed  Google Scholar 

  • Kumar A, Bello B, Reichert H (2009) Lineage-specific cell death in postembryonic brain development of Drosophila. Development 136:3433–3442

    CAS  PubMed  Google Scholar 

  • Kurusu M, Maruyama Y, Adachi Y, Okabe M, Suzuki E, Furukubo-Tokunaga K (2009) A conserved nuclear receptor, Tailless, is required for efficient proliferation and prolonged maintenance of mushroom body progenitors in the Drosophila brain. Dev Biol 326:224–236

    CAS  PubMed  Google Scholar 

  • Kurzik-Dumke U, Phannavong B, Gundacker D, Gateff E (1992) Genetic, cytogenetic and developmental analysis of the Drosophila melanogaster tumor suppressor gene lethal(2)tumorous imaginal discs (1(2)tid). Differentiation 51:91–104

    CAS  PubMed  Google Scholar 

  • Lee T, Lee, Luo L (1999) Development of the Drosophila mushroom bodies: sequential generation of three distinct types of neurons from a neuroblast. Development 126:4065–4076

    CAS  PubMed  Google Scholar 

  • Lee CY, Robinson KJ, Doe CQ (2006a) Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation. Nature 439:594–598

    CAS  PubMed  Google Scholar 

  • Lee CY, 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

    CAS  PubMed  Google Scholar 

  • Li L, Vaessin H (2000) Pan-neural prospero terminates cell proliferation during Drosophila neurogenesis. Genes Dev 14:147–151

    CAS  PubMed  Google Scholar 

  • Li HS, Wang D, Shen Q, Schonemann MD, Gorski JA, Jones KR, Temple S, Jan LY, Jan YN (2003) Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis. Neuron 40:1105–1118

    CAS  PubMed  Google Scholar 

  • Lichtneckert R, Reichert H (2008) Anteroposterior regionalization of the brain: genetic and comparative aspects. In: Technau G (ed) Brain development in Drosophila melanogaster. Landes Bioscience, Austin, pp 32–41

    Google Scholar 

  • Lin S, Lai SL, Yu HH, Chihara T, Luo L, Lee T (2010) Lineage-specific effects of Notch/Numb signaling in postembryonic development of the Drosophila brain. Development 137:43–51

    CAS  PubMed  Google Scholar 

  • Liu TH, Li L, Vaessin H (2002) Transcription of the Drosophila CKI gene dacapo is regulated by a modular array of cis-regulatory sequences. Mech Dev 112:25–36

    CAS  PubMed  Google Scholar 

  • Matsuzaki F, Koizumi K, Hama C, Yoshioka T, Nabeshima Y (1992) Cloning of the Drosophila prospero gene and its expression in ganglion mother cells. Biochem Biophys Res Commun 182:1326–1332

    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 

  • Maurange C, Gould AP (2005) Brainy but not too brainy: starting and stopping neuroblast divisions in Drosophila. Trends Neurosci 28:30–36

    CAS  PubMed  Google Scholar 

  • Maurange C, Chen L, Gould AP (2008) Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila. Cell 133:891–902

    CAS  PubMed  Google Scholar 

  • Merkle FT, Alvarez-Buylla A (2006) Neural stem cells in mammalian development. Curr Opin Cell Biol 18:704–709

    CAS  PubMed  Google Scholar 

  • Mettler U, Vogler G, Urban J (2006) Timing of identity: spatiotemporal regulation of hunchback in neuroblast lineages of Drosophila by Seven-up and Prospero. Development 133:429–437

    CAS  PubMed  Google Scholar 

  • Morrison SJ, Kimble J (2006) Asymmetric and symmetric stem cell divisions in development and cancer. Nature 441:1068–1074

    CAS  PubMed  Google Scholar 

  • Neumuller RA, Knoblich JA (2009) Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer. Genes Dev 23:2675–2699

    PubMed  Google Scholar 

  • Noctor SC, 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

    CAS  PubMed  Google Scholar 

  • Ohnuma S, Harris WA (2003) Neurogenesis and the cell cycle. Neuron 40:199–208

    CAS  PubMed  Google Scholar 

  • Parmentier ML, Woods D, Greig S, Phan PG, Radovic A, Bryant P, O’Kane CJ (2000) Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila. J Neurosci 20:RC84

    CAS  PubMed  Google Scholar 

  • Pearson BJ, Doe CQ (2003) Regulation of neuroblast competence in Drosophila. Nature 425:624–628

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Petronczki M, Knoblich JA (2001) DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila. Nat Cell Biol 3:43–49

    CAS  PubMed  Google Scholar 

  • Prokop A, Technau GM (1991) The origin of postembryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster. Development 111:79–88

    CAS  PubMed  Google Scholar 

  • Prokop A, Bray S, Harrison E, Technau GM (1998) Homeotic regulation of segment-specific differences in neuroblast numbers and proliferation in the Drosophila central nervous system. Mech Dev 74:99–110

    CAS  PubMed  Google Scholar 

  • Read TA, Hegedus B, Wechsler-Reya R, Gutmann DH (2006) The neurobiology of neurooncology. Ann Neurol 60:3–11

    CAS  PubMed  Google Scholar 

  • Rhyu MS, Jan LY, Jan YN (1994) Asymmetric distribution of Numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells. Cell 76:477–491

    CAS  PubMed  Google Scholar 

  • Schaefer M, Petronczki M, Dorner D, Forte M, Knoblich JA (2001) Heterotrimeric G proteins direct two modes of asymmetric cell division in the Drosophila nervous system. Cell 107:183–194

    CAS  PubMed  Google Scholar 

  • Schober M, Schaefer M, Knoblich JA (1999) Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts. Nature 402:548–551

    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

    CAS  PubMed Central  PubMed  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

    CAS  PubMed  Google Scholar 

  • Siegrist SE, Haque NS, Chen CH, Hay BA, Hariharan IK (2010) Inactivation of both foxo and reaper promotes long-term adult neurogenesis in Drosophila. Curr Biol 20:643–648

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Skeath JB, Carroll SB (1992) Regulation of proneural gene expression and cell fate during neuroblast segregation in the Drosophila embryo. Development 114:939–946

    CAS  PubMed  Google Scholar 

  • Skeath JB, Carroll SB (1994) The achaete–scute complex: generation of cellular pattern and fate within the Drosophila nervous system. FASEB J 8:714–721

    CAS  PubMed  Google Scholar 

  • Skeath JB, Thor S (2003) Genetic control of Drosophila nerve cord development. Curr Opin Neurobiol 13:8–15

    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

    CAS  PubMed  Google Scholar 

  • Sonoda J, Wharton RP (2001) Drosophila brain tumor is a translational repressor. Gene Dev 15:762–773

    CAS  PubMed  Google Scholar 

  • Sousa-Nunes R, Cheng LY, Gould AP (2010) Regulating neural proliferation in the Drosophila CNS. Curr Opin Neurobiol 20:50–57

    CAS  PubMed  Google Scholar 

  • Spana EP, Doe CQ (1995) The Prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila. Development 121:3187–3195

    CAS  PubMed  Google Scholar 

  • Technau GM, Berger C, Urbach R (2009) Generation of cell diversity and segmental pattern in the embryonic central nervous system of Drosophila. Dev Dyn 235:861–869

    Google Scholar 

  • Tio M, Udolph G, Yang X, Chia W (2001) cdc2 links the Drosophila cell cycle and asymmetric division machineries. Nature 409:1063–1067

    CAS  PubMed  Google Scholar 

  • Tran KD, Doe CQ (2008) Pdm and Castor close successive temporal identity windows in the NB3-1 lineage. Development 135:3491–3499

    CAS  PubMed  Google Scholar 

  • Truman JW (1990) Metamorphosis of the central nervous system in Drosophila. J Neurobiol 21:1072–1084

    CAS  PubMed  Google Scholar 

  • Truman JW, Bate M (1988) Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster. Dev Biol 125:145–157

    CAS  PubMed  Google Scholar 

  • Truman JW, Taylor BJ, Awad TA (1993) Formation of the adult nervous system. In: Bate M, Martinez-Arias A (eds) The development of Drosophila melanogaster. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 1245–1275

    Google Scholar 

  • Tsuji T, Hasegawa E, Isshiki T (2008) Neuroblast entry into quiescence is regulated intrinsically by the combined action of spatial Hox proteins and temporal identity factors. Development 135:3859–3869

    CAS  PubMed  Google Scholar 

  • Uemura T, Shepherd S, Ackerman L, Jan LY, Jan YN (1989) numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos. Cell 58:349–360

    CAS  PubMed  Google Scholar 

  • Urbach R, Technau GM (2003a) Molecular markers for identified neuroblasts in the developing brain of Drosophila. Development 130:3621–3637

    CAS  PubMed  Google Scholar 

  • Urbach R, Technau GM (2003b) Segment polarity and DV patterning gene expression reveals segmental organization of the Drosophila brain. Development 130:3607–3620

    CAS  PubMed  Google Scholar 

  • Urbach R, Technau GM (2008) Dorsoventral patterning of the brain: a comparative approach. In: Technau G (ed) Brain development in Drosophila melanogaster. Landes Bioscience, Austin, pp 43–56

    Google Scholar 

  • Urbach R, Schnabel R, Technau GM (2003) The pattern of neuroblast formation, mitotic domains and proneural gene expression during early brain development in Drosophila. Development 130:3589–3606

    CAS  PubMed  Google Scholar 

  • Vaessin H, Grell E, Wolff E, Bier E, Jan LY, Jan YN (1991) prospero is expressed in neuronal precursors and encodes a nuclear protein that is involved in the control of axonal outgrowth in Drosophila. Cell 67:941–953

    CAS  PubMed  Google Scholar 

  • Voigt A, Pflanz R, Schafer U, Jackle H (2002) Perlecan participates in proliferation activation of quiescent Drosophila neuroblasts. Dev Dyn 224:403–412

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weng M, Golden KL, Lee CY (2010) dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila. Dev Cell 18:126–135

    CAS  PubMed  Google Scholar 

  • White K, Grether ME, Abrams JM, Young L, Farrell K, Steller H (1994) Genetic control of programmed cell death in Drosophila. Science 264:677–683

    CAS  PubMed  Google Scholar 

  • Wodarz A, Huttner WB (2003) Asymmetric cell division during neurogenesis in Drosophila and vertebrates. Mech Dev 120:1297–1309

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Wu PS, Egger B, Brand AH (2008) Asymmetric stem cell division: lessons from Drosophila. Semin Cell Dev Biol 19:283–293

    CAS  PubMed  Google Scholar 

  • Yasugi T, Umetsu D, Murakami S, Sato M, Tabata T (2008) Drosophila optic lobe neuroblasts triggered by a wave of proneural gene expression that is negatively regulated by JAK/STAT. Development 135:1471–1480

    CAS  PubMed  Google Scholar 

  • Younossi-Hartenstein A, Nassif C, Green P, Hartenstein V (1996) Early neurogenesis of the Drosophila brain. J Comp Neurol 370:313–329

    CAS  PubMed  Google Scholar 

  • Yu F, Morin X, Cai Y, Yang X, Chia W (2000) Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. Cell 100:399–409

    CAS  PubMed  Google Scholar 

  • Yu F, Cai Y, Kaushik R, Yang X, Chia W (2003) Distinct roles of Galphai and Gbeta13F subunits of the heterotrimeric G protein complex in the mediation of Drosophila neuroblast asymmetric divisions. J Cell Biol 162:623–633

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Zhong W, Chia W (2008) Neurogenesis and asymmetric division. Curr Opin Neurobiol 18:4–11

    PubMed  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

    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

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Swiss NSF. I thank B. Bello for helpful comments on the manuscript.

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  1. Biozentrum, University of Basel, Klingelbergstrasse 50, CH-4056, Basel, Switzerland

    Heinrich Reichert

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  1. Heinrich Reichert
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Correspondence to Heinrich Reichert .

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  1. CNRS UMR 6061, Fac. Médecine, Université de Rennes 1, Rennes CX, 35043, France

    Jacek Z. Kubiak

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Reichert, H. (2011). Drosophila Neural Stem Cells: Cell Cycle Control of Self-Renewal, Differentiation, and Termination in Brain Development. In: Kubiak, J. (eds) Cell Cycle in Development. Results and Problems in Cell Differentiation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-19065-0_21

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