Asymmetric Cell Division in Drosophila Neuroblasts

Chwee Tat Koe, Duke‐NUS Medical School, Singapore
Hongyan Wang, Duke‐NUS Medical School, Singapore

Published online: March 2016

DOI: 10.1002/9780470015902.a0020861

Abstract

Neuronal diversity provides the basis for brain complexity. Asymmetric division of neural stem cells is a fundamental strategy for generating such diversity. Drosophila neural stem cells called neuroblasts emerge as a key model for in‐depth understanding of asymmetric division. Asymmetric division of neuroblasts is regulated by a group of highly conserved intrinsic factors through three critical steps: establishment of cortical polarity, mitotic spindle orientation and asymmetric localisation/segregation of cell fate determinants. With each round of asymmetric division, a neuroblast generates a new neuroblast to self‐renew and a ganglion mother cell (GMC) that divides terminally giving rise to two neurons. In addition, neuroblasts acquire different temporal identities that contribute to the differential neurons subtypes generated.

Key Concepts

  • Asymmetric cell division is regulated by intrinsic machinery.
  • Par complex establishes cortical polarity of neuroblasts.
  • Pins–Gαi complex regulates spindle orientation.
  • Basal cell fate determinants promote neuronal differentiation.
  • Cell cycle regulators regulate asymmetric division of neuroblasts.
  • Positioning of cleavage furrow is regulated by two temporally independent pathways.
  • Temporal regulation of neuroblasts generates neuronal diversity.

Keywords: neuroblasts; asymmetric cell division; cortical polarity; spindle orientation; asymmetric segregation; temporal regulation; cell cycle regulators; cleavage furrow

Figure 1. Intrinsic regulation of neuroblast asymmetric division. Apical (green) and basal (red) proteins are asymmetrically localised at the cortex of mitotic neuroblasts. The Par complex, which comprises Baz, Par‐6 and aPKC, establishes cell polarity. Several proteins including PP2A, AurA, Lgl, Cdc42, Zif, Dap160 and Clueless (Clu) regulate the Par complex. The Gαi–Pins–Loco complex, which is linked through Insc to the Par complex, regulates mitotic spindle orientation either through Dlg–Khc73 complex or Mud. In addition, apical localisation of Mud is regulated by Gαi–Pins complex and Ctp–Ana2 complex. Basally localised Mira–Pros–Brat complex and Pon–Numb complex regulate differentiation in ganglion mother cell independent of each other. Basal localisation of Numb and Mira is regulated through direct phosphorylation by aPKC and/or indirectly through aPKC‐mediated phosphorylation of Lgl. Localisation of Mira is also regulated by PP4 subunit Flfl while Polo and PP2A regulate Numb localisation either directly or indirectly through Pon. Actomyosin‐dependent pathway (through Zip and Jar) also partially regulates localisation of basal complexes.
Figure 2. Type I and type II neuroblast lineages in Drosophila larval brain. Larval brain is composed of two brain hemispheres and a ventral nerve cord (VNC). Each brain hemisphere contains an optic lobe region that develops into the adult fly visual system and a central brain region where type I and type II neuroblasts lineages reside. Type I neuroblasts undergo asymmetric division to self‐renew and to generate a smaller daughter cell known as ganglion mother cell (GMC) that undergoes a terminal division to form two neurons/glia. On the other hand, with each asymmetric division, a type II neuroblast generates a new neuroblast and an intermediate neural progenitor (INP). Newly formed INPs are immature and will undergo a maturation process characterised by the gain of Asense (Ase). In mature form, INPs possess limited proliferative ability and can undergo 8–10 rounds of asymmetric division to self‐renew and generate GMCs that give rise to neurons/glia.
Figure 3. Temporal regulation of neuroblasts. (a) Temporal patterning of VNC neuroblasts. A series of transcription factors regulates the identity of neuroblasts and their neural progeny. NBs express different transcription factors at different temporal point that are inherited by the GMCs and neurons. Embryonic NBs consecutively express Hunchback (HB, yellow), Seven up (Svp, orange), Kruppel (Kr, blue), Pdm1/2 (Pdm, red) and lastly, Castor (Cas, green) before entering quiescence. At larval stage, NBs resume Cas expression but transit to Svp expression shortly after. Transition to Svp induces transition from large Chinmo expressing neurons to small Broad complex (Br–C) expressing neurons. However, temporal transcription factors expressed after Svp in larval and pupal stage have yet been identified. (b) Temporal patterning of DM2‐3 type II neuroblasts. (1) Neuroblast temporal cascade. DM1‐3 type II neuroblasts express Diachete (D) and Castor (cas) at 24 h after larval hatching (ALH), while Svp is transiently expressed at 48 h ALH. Temporal factor express at later stage is unknown. (2) INP temporal cascade. In addition, INPs generated from DM2‐6 type II neuroblasts also exhibit temporal patterning. INPs sequentially express D, Grainyhead (Grh) and Eyeless (Ey) over time. Ey+ old INPs generate from early D+/Cas+ neuroblasts produce either Repo+ (Reverse polarity) glia or Toy+ (Twin of eyeless) neurons. Late neuroblasts derived D+ young INPs produce D+ or Bsh+ (Brain‐specific homeobox) progenies.
Figure 4. Implications of asymmetric cell division with cancer formation. (a) A wild‐type neuroblast undergoes asymmetric division to self‐renewal and to generate a GMC that gives rise two neurons/glia. (b) Altered asymmetric proteins segregation, for instance by loss of aurora‐A, can generate two neuroblast‐like daughter cells with self‐renewing ability, leading to neuroblast overgrowth. (c) Spindle misorientation can cause missegregation of asymmetrically localised proteins, resulting in neuroblasts overgrowth.
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References

Almeida MS and Bray SJ (2005) Regulation of post‐embryonic neuroblasts by Drosophila Grainyhead. Mechanisms of Development 122: 1282–1293.

Andersen RO , Turnbull DW , Johnson EA and Doe C (2012) Sgt1 acts via an LKB1/AMPK pathway to establish cortical polarity in larval neuroblasts. Developmental Biology 363 (1): 258–265.

Ang XL and Wade Harper J (2005) SCF‐mediated protein degradation and cell cycle control. Oncogene 24 (17): 2860–2870.

Apitz H and Salecker I (2014) A challenge of numbers and diversity: Neurogenesis in the Drosophila optic lobe. Journal of Neurogenetics. DOI: 10.3109/01677063.2014.922558.

Arama E , Dickman D , Kimchie Z , Shearn A and 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.

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

Atwood SX and Prehoda KE (2009) aPKC phosporlyates Miranda to polarise fate determinants during neuroblast asymmetric cell division. Current Biology 19: 723–729.

Barros CS , Phelps CB and Brand AH (2003) Drosophila non‐muscle myosin II promotes the asymmetric segregation of cell fate determinants by cortical exclusion rather than active transport. Developmental Cell 5: 829–840.

Bayraktar OA and Doe CQ (2013) Combinatorial temporal patterning in progenitors expands neural diversity. Nature 498 (7455): 449–455.

Bayraktar OA , Boone JQ , Drummond ML and Doe CQ (2010) Drosophila type II neuroblast lineages keep Prospero levels low to generate large clones that contribute to the adult brain central complex. Neural Developmental 5: 26.

Bello BC , Hirth F and 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.

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

Bello BC , Izergina N , Caussinus E and Reichert H (2008) Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development. Neural Developmental 3: 5 DOI: 10.1186/1749-8104-3-5.

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

Betschinger J , Mechtler K and Knoblich JA (2006) Asymmetric segregation of the tumour suppressor brat regulates self‐renewal in Drosophila neural stem cells. Cell 124 (6): 1241–1253.

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

Bowman SK , Neumüller RA , Novatchkova M , Du Q and Knoblich JA (2006) The Drosophila NuMA homolog mud regulates spindle orientation in asymmetric cell division. Developmental Cell 10 (6): 731–742.

Bowman SK , Rolland V , Betschinger J , et al. (2008) The tumor suppressors Brat and Numb regulate transit‐amplifying neuroblast lineages in Drosophila. Developmental Cell 14: 535–546.

Bray SJ , Burke B , Brown NH and Hirsh J (1989) Embryonic expression pattern of a family of Drosophila proteins that interact with a central nervous system regulatory element. Genes and Development 3: 1130–1145.

Broadus J and Doe CQ (1997) Extrinsic cues, intrinsic cues and mircofilaments regulate asymmetric protein localization in Drosophila neuroblasts. Current Biology 7 (11): 827–835.

Brody T and Odenwald WF (2000) Programmed transformations in neuroblast gene expression during Drosophila CNS lineage development. Developmental Biology 226 (1): 34–44.

Bultje RS , Castaneda‐Castellanos DR , Jan LY , et al. (2009) Mammalian Par3 regulates progenitor cell asymmetric division via Notch signaling in the developing neocortex. Neuron 63: 189–202.

Cabernard C and Doe CQ (2009) Apical/basal spindle orientation is required for neuroblast homeostasis and neuronal differentiation in Drosophila . Developmental Cell 17: 134–141.

Cabernard C , Prehoda KE and Doe CQ (2010) A spindle‐independent cleavage furrow positioning pathway. Nature 467: 91–95.

Carmena M , Wheelock M , Funabiki H and Earnshaw WC (2012) The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis. Nature Reviews Molecular Cell Biology 13: 789–803.

Caussinus E and Gonzalez C (2005) Induction of tumor growth by altered stem‐cell asymmetric division in Drosophila melanogaster . Nature Genetics 37 (10): 1125–1129.

Cenci C and 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.

Ceron J , Tejedor FJ and Moya F (2006) A primary cell culture of Drosophila postembryonic larval neuroblasts to study cell cycle and asymmetric division. European Journal of Cell Biology 85: 567–575.

Chabu C and Doe CQ (2008) Dap160/intersectin binds and activates aPKC to regulate cell polarity and cell cycle progression. Development 135 (16): 2739–2746.

Chabu C and Doe CQ (2009) Twins/PP2A regulates aPKC to control neuroblast cell polarity and self‐renewal. Developmental Biology 330 (2): 399–405.

Chang KC , Garcia‐Alvarez G , Somers G , et al. (2010) Interplay between the transcription factor Zif and aPKC regulates neuroblast polarity and self‐renewal. Developmental Cell 19: 778–785.

Chang KC , Wang C and Wang H (2012) Balancing self‐renewal and differentiation by asymmetric division: insights from brain tumor suppressors in Drosophila neural stem cells. BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology 34: 301–310.

Chenn A and McConnell SK (1995) Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis. Cell 82: 631–641.

Chia W , Somers WG and Wang H (2008) Drosophila neuroblast asymmetric divisions: cell cycle regulators, asymmetric protein localization and tumorigenesis. Journal of Cell Biology 180 (2): 267–72.

Choksi SP , Southall TD , Bossing T , et al. (2006) Prospero acts as a binary switch between self‐renewal and differentiation in Drosophila neural stem cell. Developmental Cell 11 (6): 775–789.

Colonques J , Ceron J , Reichert H and Tejedor FJ (2011) A transient expression of Prospero promotes cell cycle exit of Drosophila postembryonic neurons through the regulation of Dacapo . PLoS ONE 6 (4): e19342.

Conduit PT and Raff JW (2010) Cnn dynamics drive centrosome size asymmetry to ensure daughter centriole retention in Drosophila neuroblasts. Current Biology 20 (24): 2187–2192.

Culurgioni S , Alfieri A , Pendolino V , Laddomada F and Mapelli M (2011) Inscuteable and NuMA proteins bind competitively to Leu‐Gly‐Asn repeat‐enriched protein (LGN) during asymmetric cell divisions. Proceedings of the National Academy of Sciences of the United States of America 108 (52): 20998–21003.

David NB , Martin CA , Segalen M , et al. (2005) Drosophila Ric‐8 regulates Galphai cortical localization to promote Galphai‐dependent planar orientation of the mitotic spindle during asymmetric cell division. Nature Cell Biology 7: 1083–1090.

Dong Z , Yang N , Yeo SY , Chitnis A and Guo S (2012) Intralineage directional notch signaling regulates self‐renewal and differentiation of asymmetrically dividing radial glia. Neuron 74: 65–78.

Du Q , Stukenberg PT and Macara IG (2001) A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nature Cell Biology 3 (12): 1069–1075.

Du Q and Macara IG (2004) Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119 (4): 503–516.

Dyer MA , Livesey FJ , Cepko CL and Oliver G (2003) Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nature Genetics 34 (1): 53–58.

Eckley DM , Ainsztein AM , Mackay AM , Goldberg IG and Earnshaw WC (1997) Chromosomal proteins and cytokinesis: patterns of cleavage furrow formation and inner centromere protein positioning in mitotic heterokaryons and mid‐anaphase cells. Journal of Cell Biology 136: 1169–1183.

Erben V , Waldhuber M , Langer D , et al. (2008) Asymmetric localization of the adapter protein Miranda in neuroblasts is achieved by diffusion and sequential interaction of Myosin II and VI. Journal of Cell Science 121: 1403–1414.

Goh LH , Zhou X , Lee MC , et al. (2013) Clueless regulates aPKC activity and promotes self‐renewal cell fate in Drosophila lgl mutant larval brains. Developmental Biology 381 (2): 353–364.

Gonzalez C (2007) Spindle orientation, asymmetric division and tumour suppression in Drosophila stem cells. Nature Reviews Genetics 8 (6): 462–472.

Gotz M and Huttner WB (2005) The cell biology of neurogenesis. Nature Reviews Molecular Cell Biology 6: 777–788.

Grosskortenhaus R , Pearson BJ , Marusich A and Doe CQ (2005) Regulation of temporal identity transitions in Drosophila neuroblasts. Developmental Cell 8 (2): 193–202.

Hartenstein V and Campos‐Ortega JA (1984) Early neurogenesis in wild‐type Drosophila melanogaster . Roux's Archives of Developmental Biology 193: 308–325.

Hartenstein V and Wodarz A (2013) Initial neurogenesis in Drosophila . Interdisciplinary Reviews Development Biology 2 (5): 701–721.

Heisenberg M (1998) What do the mushroom bodies do for the insect brain? An introduction. Learning and Memory 5 (1): 1–10.

Homem CCF and Knoblich JA (2012) Drosophila neuroblasts: a model for stem cell biology. Development 139: 4297–4310.

Homem CCF , Steinmann V , Burkard TR , et al. (2014) Ecdysone and mediator change energy metabolism to terminate proliferation in Drosophila neural stem cells. Cell 158 (4): 874–888.

Huttner WB and Brand M (1997) Asymmetric division and polarity of neuroepithelial cells. Current Opinion in Neurobiology 7: 29–39.

Huttner WB and Kosodo Y (2005) Symmetric versus asymmetric cell division during neurogenesis in the developing vertebrate central nervous system. Current Opinion in Neurobiology 17 (6): 648–657.

Ikeshima‐Kataoka H , Skeath J , Nabeshuma Y , Doe CQ and Matsuzaki F (1997) Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions. Nature 390: 625–629.

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

Ito K and Hotta Y (1991) Proliferation pattern of postembryonic neuroblasts in the brain of Drosophila melanogaster . Developmental Biology 149: 134–148.

Izaki T , Kamakura S , Kohjima M and Sumimoto H (2006) Two forms of human Inscuteable‐related protein that links Par3 to the Pins homologues LGN and AGS3. Biochemical and Biophysical Research Communications 341 (4): 1001–1006.

Izumi Y , Ohta N , Hisata K , Raabe T and Matsuzaki F (2006) Drosophila Pins‐binding protein Mud regulates spindle polarity coupling and centrosome organization. Nature Cell Biology 8 (6): 586–593.

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

Januschke J , Llamazares S , Reina J and Gonzalez C (2011) Drosophila neuroblasts retain the daughter centrosome. Nature Communications 2: 243.

Joberty G , Petersen C , Gao L and Macara IG (2000) The cell polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nature Cell Biology 2: 531–539.

Johnston CA , Hirono K , Prehoda KE and Doe C (2009) Identification of an Aurora‐A/PinsLinker/Dlg spindle orientation pathway using induced cell polarity in S2 cells. Cell 138 (6): 1150–1163.

Kambadur R , Koizumi K , Stivers C , et al. (1998) Regulation of POU genes by castor and hunchback establishes layered compartments in the Drosophila CNS. Genes and Development 12 (2): 246–260.

Kenyon FC (1986) The brain of the bee—a preliminary contribution to the morphology of the nervous system of the Arthropoda . Journal of Comparative Neurology 6: 134–210.

Konno D , Shioi G , Shitamukai A , et al. (2008) Neuroepithelial progenitors undergo LGN‐dependent planar divisions to maintain self‐renewability during mammalian neurogenesis. Nature Cell Biology 10: 93–101.

Kosodo Y , Roper K , Haubensak W , et al. (2004) Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells. EMBO Journal 23: 2314–2324.

Krahn MP , Egger‐Adam D and Wodarz A (2009) PP2A antagonises phosphorylation of Bazooka by PAR‐1 to control apical‐basal polarity in dividing embryonic neuroblasts. Developmental Cell 16 (6): 901–908. DOI: 10.1016/j.devcel.2009.04.011.

Krahn MP , Klopfenstein DR , Fischer N and Wodarz A (2010) Membrane targeting of Baz/Par‐3 is mediated by direct binding to phosphoinositide lipids. Current Biology 20 (7): 636–642.

Kraut R , Chia W , Jan LY , Jan YN and Knoblich JA (1996) Role of Inscuteable in orienting asymmetric cell divisions in Drosophila . Nature 383 (6595): 50–55.

Kriegstein A and Alvarez‐Buylla A (2009) The glial nature of embryonic and adult neural stem cells. Annual Review of Cell and Developmental Biology 32: 149–184.

Kuchinke U , Grawe F and Knust E (1998) Control of spindle orientation in Drosophila by the Par‐3‐related PDZ‐domain protein Bazooka. Current Biology 8 (25): 1357–1365.

Lancaster MA and Knoblich JA (2012) Spindle orientation in mammalian cerebral cortical development. Current Opinion in Neurobiology 22: 737–746.

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

Lee CY , Wilkinson BD , Siegrist SE , Wharton RP and Doe CQ (2006b) Brat is a Mranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self‐renewal. Developmental Cell 10 (4): 441–449.

Lin D , Edwards AS , Fawcett JP , et al. (2000) A mammalian PAR‐3‐PAR‐6 complex implicated in Cdc42/Rac1 and aPKC signaling and cell polarity. Nature Cell Biology 2: 540–547.

Li S , Wang C , Sandanaraj E et al. (2014) The SCF Slimb E3 ligase complex regulates asymmetric division to inhibit neuroblast overgrowth. EMBO Reports 15 (2): 165–174.

Lu B , Ackerman L , Jan LY and Jan YN (1999) Modes of protein movement that lead to the asymmetric localization of partner of Numb during Drosophila neuroblast division. Molecular Cell 4: 883–891.

Maurange C (2012) Temporal specification of neural stem cells: insights from Drosophila neuroblasts. Current Topics in Developmental Biology 98: 199–228.

Maurange C , Cheng L and Gould AP (2008) Temporal transcription factors and their targets schedule the end of neurogenesis in Drosophila . Cell 133 (5): 891–902.

Nipper RW , Siller KH , Smith NR , Doe CQ and Prehoda KE (2007) Galphai generates multiple Pins activation states to link cortical polarity and spindle orientation in Drosophila neuroblasts. Proceedings of the National Academy of Sciences of the United States of America 104 (36): 14306–14311.

Nishimura T , Kato K , Yamaguchi T , et al. (2004) Role of the PAR‐3‐KIF3 complex in the establishment of neuronal polarity. Nature Cell Biology 6 (4): 328–334.

Ogawa H , Ohta N , Moon W and Matsuzaki F (2009) Protein phosphatase 2A negatively regulates aPKC signaling by modulating phosphorylation of Par‐6 in Drosophila neuroblast asymmetric divisions. Journal of Cell Science 122 (18): 3242–3249. DOI: 10.1242/jcs.050955.

Ouyang Y , Petritsch C , Wen H , et al. (2011) Dronc caspase exerts a non‐apoptotic function to restrain phospho‐Numb‐induced ectopic neuroblast formation in Drosophila . Development 138: 2185–2196.

Parmentier ML , Woods D , Greig S , et al. (2000) Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila . Journal of Neuroscience 20 (14): RC84.

Petersen PH , Zou K , Hwang JK , et al. (2002) Progenitor cell maintenance requires numb and numblike during mouse neurogenesis. Nature 419 (6910): 929–934.

Petersen PH , Zou K , Krauss S and Zhong W (2004) Continuing role for mouse Numb and Numbl in maintaining progenitor cells during cortical neurogenesis. Nature Neuroscience 7 (8): 803–811.

Peterson C , Carney GE , Taylor BJ and White K (2002) Reaper is required for neuroblast apoptosis during Drosophila development. Development 129: 1467–1476.

Petritsch C , Tavosanis G , Turck CW , Jan LY and Jan YN (2003) The Drosophila myosin VI Jaguar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts. Developmental Cell 4 (2): 273–281.

Postiglione MP , Juschke C , Xie Y , et al. (2011) Mouse inscuteable induces apical‐basal spindle orientation to facilitate intermediate progenitor generation in the developing neocortex. Neuron 72 (2): 269–284.

Poulson ND and Lechler T (2010) Robust control of mitotic spindle orientation in the developing epidermis. Journal of Cell Biology 191 (5): 915–922.

Rebollo E , Sampaio P , Januschke J , et al. (2007) Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. Developmental Cell 12 (3): 467–474.

Rolls MM , Albertson R , Shih HP , Lee CY and Doe CQ (2003) Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. The Journal of Cell Biology 163: 1089–1098.

Roth M , Roubinet C , Ifflander N , Ferrand A and Cabernard C (2015) Asymmetrically dividing neuroblasts utilise two spatially and temporally independent cytokinesis pathways. Nature Communications 6: 6551.

Rusan NM and Peifer M (2007) A role for a novel centrosome cycle in asymmetric cell division. Journal of Cell Biology 177 (1): 13–20.

Schaefer M , Shevchenko A and Knoblich JA (2000) A protein complex containing inscuteable and the Gα‐binding protein pins orients asymmetric cell divisions in Drosophila . Current Biology 10 (7): 353–362.

Schaefer M , Petronczki M , Dorner D , Forte M and Knoblich JA (2001) Heterotrimeric G proteins direct two modes of asymmetric cell division in the Drosophila nervous system. Cell 107 (2): 183–194.

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

Schwamborn JC , Berezikov E and Knoblich JA (2009) The TRIM‐NHL protein TRIM32 activates microRNAs and prevents self‐renewal in mouse neural progenitors. Cell 136 (5): 913–925.

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

Shen C‐P , Knoblich JA , Chan Y , et al. (1998) Miranda as a multidomain adapter linking apically localized Inscuteable and basally localised Satufen and Prospero during asymmetric cell division in Drosophila . Genes and Development 12: 1837–1846.

Shitamukai A , Konno D and 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. Journal of Neuroscience 31: 3683–3695.

Shitamukai A and Matsuzaki M (2012) Control of asymmetric cell division of mammalian neural proenitors. Development Growth and Differentiation 54: 277–286.

Siegrist SE and Doe CQ (2005) Microtubule‐induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell 123 (7): 1323–1335.

Siller KH , Cabernard C and Doe CQ (2006) The NuMA related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts. Nature Cell Biology 8 (6): 594–600.

Skeath JB and Doe CQ (1998) Sanpodo and Notch acts in opposition to Numb to distinguish sibling neuron fates in the Drosophila nerve cord development. Development 125: 1857–1865.

Smith CA , Lau KM , Rahmani Z , et al. (2007) aPKC‐mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. The EMBO Journal 26: 468–480.

Somers WG and Saint R (2003) A RhoGEF and Rho family GTPase‐activating protein complex links the contractile ring to cortical microtubules at the onset of cytokinesis. Developmental Cell 4: 29–39.

Sousa‐Nunes R , Chia W and Somers WG (2009) Protein phosphatase 4 mediates localization of the Miranda complex during Drosophila neuroblast asymmetric divisions. Genes and Development 23: 359–372.

Sousa‐Nunes R and Somers WG (2013) Mechanisms of asymmetric progenitor divisions in the Drosophila central nervous system. Advances in Experimental Medicine and Biology: 786. DOI: 10.1007/978-94-007-6621-16.

Sprecher SG , Reichert H and Hartenstein V (2007) Gene expression patterns in primary neuronal clusters of the Drosophila embryonic brain. Gene Expression Patterns 7: 584–595.

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

Wang H , Ng KH , Qian H , et al. (2005) Ric‐8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins. Nature Cell Biology 7: 1091–1098.

Wang H , Somers GW , Bashirullah A , et al. (2006) Aurora‐A acts as a tumor suppressor and regulates self‐renewal of Drosophila neuroblasts. Genes and Development 20 (24): 3453–3463.

Wang H , Ouyang Y , Somers WG , Chia W and Lu B (2007) Polo inhibits progenitor self‐renewal and regulates Numb asymmetry by phosphorylating Pon. Nature 449 (7158): 96–100.

Wang C , Chang KC , Somers G , et al. (2009) Protein phosphatase 2A regulates self‐renewal of Drosophila neural stem cells. Development 136 (13): 2287–2296.

Wang C , Li S , Januschke J , et al. (2011) An Ana2/Ctp/Mud complex regulates spindle orientation in Drosophila neuroblasts. Developmental Cell 21: 520–533.

Weng M , Golden KL and Lee CY (2010) dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila . Developmental Cell 18 (1): 126–135.

Weng M and Lee CY (2011) Keeping neural progenitor cells on a short leash during Drosophila neurogenesis. Current Opinion in Neurobiology 21 (1): 36–42.

White K , Grether ME , Abrams JM , et al. (1994) Genetic control of programmed cell death in Drosophila . Science 264: 677–683.

White EA and Glotzer M (2012) Centralspindlin: at the heart of cytokinesis. Cytoskeleton (Hoboken) 69: 882–892.

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

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

Yamanaka T , Horikoshi Y , Suzuki A , et al. (2001) PAR‐6 regulates aPKC activity in a novel way and mediates cell‐cell contact induced formation of the epithelial junctional complex. Genes to Cells 6: 721–731.

Yong KJ and Yan B (2011) The relevance of symmetric and asymmetric cell division to human central nervous system diseases. Journal of Clinical Neurology 18: 458–463.

Yoshiura S , Ohta N and Matsuzaki F (2011) Tre1 GPCR signaling orients stem cell divisions in the Drosophila central nervous system. Dev. Cell 22 (1): 79–91.

Yu F , Morin X , Cai Y , Yang X and 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 (4): 399–409.

Yu F , Wang H , Qian H , et al. (2005) Locomotion defects, together with Pins, regulates heterotrimeric G‐protein signaling during Drosophila neuroblast asymmetric divisions. Genes and Development 19 (11): 1341–1353.

Yu F , Kuo CT and Jan YN (2006) Drosophila neuroblast asymmetric cell division: recent advances and implications for stem cell biology. Neuron 51 (1): 13–20.

Yuzawa S , Kamakura S , Iwakiri Y , Hayase J and Sumimoto H (2011) Structural basis for interaction between the conserved cell polarity proteins Inscuteable and Leu‐Gly‐Asn repeat‐enriched protein (LGN). Proceedings of the National Academy of Sciences of the United States of America 108 (48): 19210–16215.

Zeng C (2000) NuMA: a nuclear protein involved in mitotic centrosome function. Microscopy Research and Technique 49 (5): 467–477.

Zhong W , Feder JN , Jiang MM , Jan LY , et al. (1996) Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis. Neuron 17 (1): 43–53.

Zhu J , Wen W , Zheng Z , Shang Y , et al. (2011) LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in asymmetric cell division for the Par3/mInsc/LGN and Galphai/LGN/NuMA pathways. Molecular Cell 43 (3): 418–431.

Zigman M , Cayouette M , Charalambous C , Schleiffer A , et al. (2005) Mammalian inscuteable regulates spindle orientation and cell fate in the developing retina. Neuron 48 (4): 539–545.

Further Reading

Kohwi M and Doe CQ (2013) Temporal fate specification and neural progenitor competence during development. Nature Reviews Neuroscience 14 (12): 823–838.

Peyre E and Morin X (2012) An oblique view on the role of spindle orientation in vertebrate neurogenesis. Development, Growth & Differentiation 54 (3): 287–305. DOI: 10.1111/j.1440-169X.2012.01350.x.

Taverna E , Gotz M and Huttner WB (2014) The cell biology of neurogenesis: toward an understanding of the development and evolution of the neocortex. Annual Review of Cell and Developmental Biology 30: 465–502.

Related Sub-Topics:

Cell Cycle | Intracellular and Extracellular Signalling | Genes, Molecules and Cellular Processes | Nervous System Development | Developmental Models | Development of Invertebrate Nervous System
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Article Title: Asymmetric Cell Division in Drosophila Neuroblasts
 
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Koe, Chwee Tat, and Wang, Hongyan(Mar 2016) Asymmetric Cell Division in Drosophila Neuroblasts. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020861]