Advertisement

Cell and Tissue Research

, Volume 359, Issue 1, pp 33–45 | Cite as

Control of neural stem cell self-renewal and differentiation in Drosophila

  • Kyung Hwa Kang
  • Heinrich Reichert
Review

Abstract

The neural stem cells of Drosophila, called neuroblasts, have the ability to self-renew and at the same time produce many different types of neurons and glial cells. In the central brain and ventral ganglia, neuroblasts are specified and delaminate from the neuroectoderm during embryonic development under the control of proneural and neurogenic genes. In contrast, in the optic lobes, neuroepithelial cells are transformed into neuroblasts postembryonically by a spatial wave of proneural gene expression. Central brain and ventral nerve cord neuroblasts manifest a short embryonic proliferation period followed by a stage of quiescence and then undergo a prolonged postembryonic proliferation period during which most of the differentiated neurons of the adult CNS are generated. While most neuroblasts belong to a type I class that produces neuronal lineages through non-self-renewing ganglion mother cells, a small subset of type II neuroblasts generates exceptionally large neuronal lineages through self-renewing intermediate progenitor cells that have a transit amplifying function. All neuroblasts in the CNS generate their neural progeny through an asymmetric cell division mode in which the interplay of apical complex and basal complex molecules in the mitotically active progenitor results in the segregation of cell fate determinants into the smaller more differentiated daughter cell. Defects in this molecular control of asymmetric cell division in neuroblasts can result in brain tumor formation. Proliferating neuroblast lineages in the developing CNS utilize transcription factor cascades as a generic mechanism for temporal patterning and birth order-dependent determination of differential neural cell fate. This contributes to the generation of a remarkable diversity of cell types in the developing CNS from a surprisingly small set of neural stem cell-like precursors.

Keywords

Neuroblast Asymmetric cell division Proliferation Tumor Temporal series 

Abbreviations

aPKC

Atypical protein kinase C

CNS

Central nerve system

Gαi

G protein α i subunit 65A

INP

Intermediate neural progenitor

Mud

Mushroom body defect

Par3

Partitioning defect 3

Par6

Partitioning defect 6

Pins

Partner of Inscuteable

Pon

Partner of Numb

Notes

Acknowledgments

We thank Yanrui Jiang for critical reading of the manuscript. This work was supported by grants from the Swiss National Research Program 63 (4063 L 128006) and the Swiss National Science Foundation (31003A 140607) as well as by grants from the Global Research Laboratory Program (NRF-2009-00424), Brain Research Program (NRF-2009-0081465), and Stem Cell Research Program (NRF-2006-2004289) of the Korean Ministry of Science, ICT, and Future Planning (MSIP).

References

  1. Almeida MS, Bray SJ (2005) Regulation of post-embryonic neuroblasts by Drosophila Grainyhead. Mech Dev 122:1282–1293PubMedGoogle Scholar
  2. Artavanis-Tsakonas S, Simpson P (1991) Choosing a cell fate: a view from the Notch locus. Trends Genetics 7:403–408Google Scholar
  3. Atwood SX, Prehoda KE (2009) aPKC Phosphorylates Miranda to polarize fate determinants during neuroblast asymmetric cell division. Curr Biol 19:723–729PubMedCentralPubMedGoogle Scholar
  4. Baumgardt M, Karlsson D, Terriente J, Diaz-Benjumea FJ, Thor S (2009) Neuronal subtype specification within a lineage by opposing temporal feed-forward loops. Cell 139:969–982PubMedGoogle Scholar
  5. Bayraktar OA, Boone JQ, Drummond ML, 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 Dev 5:26PubMedCentralPubMedGoogle Scholar
  6. Bayraktar OA, Doe CQ (2013) Combinatorial temporal patterning in progenitors expands neural diversity. Nature 498:449–455PubMedCentralPubMedGoogle Scholar
  7. Beaucher M, Goodliffe J, Hersperger E, Trunova S, Frydman H, Shearn A (2007) Drosophila brain tumor metastases express both neuronal and glial cell type markers. Dev Biol 301:287–297PubMedCentralPubMedGoogle Scholar
  8. Bello B, Holbro N, Reichert H (2007) Polycomb group genes are required for neural stem cell survival in postembryonic neurogenesis of Drosophila. Development 134:1091–1099PubMedGoogle Scholar
  9. 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 133:2639–2648PubMedGoogle Scholar
  10. 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 37:209–219PubMedGoogle Scholar
  11. Bello BC, Izergina N, Caussinus E, Reichert H (2008) Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development. Neural Dev 3:5PubMedCentralPubMedGoogle Scholar
  12. Benito-Sipos J, Estacio-Gomez A, Moris-Sanz M, Baumgardt M, Thor S, Diaz-Benjumea FJ (2010) A genetic cascade involving klumpfuss, nab and castor specifies the abdominal leucokinergic neurons in the Drosophila CNS. Development 137:3327–3336PubMedGoogle Scholar
  13. Benito-Sipos J, Ulvklo C, Gabilondo H, Baumgardt M, Angel A, Torroja L, Thor S (2011) Seven up acts as a temporal factor during two different stages of neuroblast 5-6 development. Development 138:5311–5320PubMedGoogle Scholar
  14. Berger C, Harzer H, Burkard TR, Steinmann J, van der Horst S, Laurenson AS, Novatchkova M, Reichert H, Knoblich JA (2012) FACS purification and transcriptome analysis of drosophila neural stem cells reveals a role for Klumpfuss in self-renewal. Cell Rep 2:407–418PubMedCentralPubMedGoogle Scholar
  15. Betschinger J, Mechtler K, Knoblich JA (2003) The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 422:326–330PubMedGoogle Scholar
  16. Betschinger J, Mechtler K, Knoblich JA (2006) Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell 124:1241–1253PubMedGoogle Scholar
  17. Boone JQ, Doe CQ (2008) Identification of Drosophila type II neuroblast lineages containing transit amplifying ganglion mother cells. Dev Neurol 68:1185–1195Google Scholar
  18. Bossing T, Udolph G, Doe CQ, Technau GM (1996) The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm. Dev Biol 179:41–64PubMedGoogle Scholar
  19. Bowman SK, Rolland V, Betschinger J, Kinsey KA, Emery G, Knoblich JA (2008) The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev Cell 14:535–546PubMedCentralPubMedGoogle Scholar
  20. Broadus J, Doe CQ (1995) Evolution of neuroblast identity: seven-up and prospero expression reveal homologous and divergent neuroblast fates in Drosophila and Schistocerca. Development 121:3989–3996PubMedGoogle Scholar
  21. Brody T, Odenwald WF (2000) Programmed transformations in neuroblast gene expression during Drosophila CNS lineage development. Dev Biol 226:34–44PubMedGoogle Scholar
  22. Buescher M, Hing FS, Chia W (2002) Formation of neuroblasts in the embryonic central nervous system of Drosophila melanogaster is controlled by SoxNeuro. Development 129:4193–4203PubMedGoogle Scholar
  23. Campos-Ortega JA (1993) Mechanisms of early neurogenesis in Drosophila melanogaster. J Neurobiol 24:1305–1327PubMedGoogle Scholar
  24. Caussinus E, Gonzalez C (2005) Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet 37:1125–1129PubMedGoogle Scholar
  25. 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 132:3835–3845PubMedGoogle Scholar
  26. Chang KC, Wang C, Wang H (2012) Balancing self-renewal and differentiation by asymmetric division: insights from brain tumor suppressors in Drosophila neural stem cells. BioEssays 34:301–310PubMedGoogle Scholar
  27. Chell JM, Brand AH (2010) Nutrition-responsive glia control exit of neural stem cells from quiescence. Cell 143:1161–1173PubMedCentralPubMedGoogle Scholar
  28. Choksi SP, Southall TD, Bossing T, Edoff K, de Wit E, Fischer BE, 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 11:775–789PubMedGoogle Scholar
  29. Colombani J, Andersen DS, Leopold P (2012) Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing. Science 336:582–585PubMedGoogle Scholar
  30. Doe CQ (1992) Molecular markers for identified neuroblasts and ganglion mother cells in the Drosophila central nervous system. Development 116:855–863PubMedGoogle Scholar
  31. Doe CQ (2008) Neural stem cells: balancing self-renewal with differentiation. Development 135:1575–1587PubMedGoogle Scholar
  32. Doe CQ, Technau GM (1993) Identification and cell lineage of individual neural precursors in the Drosophila CNS. Trends Neurosci 16:510–514PubMedGoogle Scholar
  33. 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 2:1PubMedCentralPubMedGoogle Scholar
  34. Egger B, Chell JM, Brand AH (2008) Insights into neural stem cell biology from flies. Philos Trans R Soc Lond B 363:39–56Google Scholar
  35. Egger B, Gold KS, Brand AH (2010) Notch regulates the switch from symmetric to asymmetric neural stem cell division in the Drosophila optic lobe. Development 137:2981–2987PubMedCentralPubMedGoogle Scholar
  36. Egger B, Gold KS, Brand AH (2011) Regulating the balance between symmetric and asymmetric stem cell division in the developing brain. Fly 5:237–241PubMedGoogle Scholar
  37. Fernandez-Hernandez I, Rhiner C, Moreno E (2013) Adult neurogenesis in Drosophila. Cell Reports 3:1857–1865PubMedGoogle Scholar
  38. Grosskortenhaus R, Pearson BJ, Marusich A, Doe CQ (2005) Regulation of temporal identity transitions in Drosophila neuroblasts. Dev Cell 8:193–202PubMedGoogle Scholar
  39. Grosskortenhaus R, Robinson KJ, Doe CQ (2006) Pdm and Castor specify late-born motor neuron identity in the NB7-1 lineage. Genes Dev 20:2618–2627PubMedCentralPubMedGoogle Scholar
  40. Hartenstein V, Wodarz A (2013) Initial neurogenesis in Drosophila. Dev Biol 2:701–721Google Scholar
  41. Homem CC, Knoblich JA (2012) Drosophila neuroblasts: a model for stem cell biology. Development 139:4297–4310PubMedGoogle Scholar
  42. Ikeshima-Kataoka H, Skeath JB, Nabeshima Y, Doe CQ, Matsuzaki F (1997) Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions. Nature 390:625–629PubMedGoogle Scholar
  43. 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 106:511–521PubMedGoogle Scholar
  44. Ito K, Hotta Y (1992) Proliferation pattern of postembryonic neuroblasts in the brain of Drosophila melanogaster. Dev Biol 149:134–148PubMedGoogle Scholar
  45. Izergina N, Balmer J, Bello B, Reichert H (2009) Postembryonic development of transit amplifying neuroblast lineages in the Drosophila brain. Neural Dev 4:44PubMedCentralPubMedGoogle Scholar
  46. 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 8:586–593PubMedGoogle Scholar
  47. Januschke J, Gonzalez C (2008) Drosophila asymmetric division, polarity and cancer. Oncogene 27:6994–7002PubMedGoogle Scholar
  48. Jiang Y, Reichert H (2012) Programmed cell death in type II neuroblast lineages is required for central complex development in the Drosophila brain. Neural Dev 7:3PubMedCentralPubMedGoogle Scholar
  49. 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 12:246–260PubMedCentralPubMedGoogle Scholar
  50. Karcavich R, Doe CQ (2005) Drosophila neuroblast 7-3 cell lineage: a model system for studying programmed cell death, Notch/Numb signaling, and sequential specification of ganglion mother cell identity. J Comp Neurol 481:240–251PubMedGoogle Scholar
  51. Karcavich RE (2005) Generating neuronal diversity in the Drosophila central nervous system: a view from the ganglion mother cells. Dev Dyn 232:609–616PubMedGoogle Scholar
  52. Karlsson D, Baumgardt M, Thor S (2010) Segment-specific neuronal subtype specification by the integration of anteroposterior and temporal cues. PLoS Biol 8:e1000368PubMedCentralPubMedGoogle Scholar
  53. Knoblich JA (2008) Mechanisms of asymmetric stem cell division. Cell 132:583–597PubMedGoogle Scholar
  54. Komori H, Xiao Q, McCartney BM, Lee CY (2014) Brain tumor specifies intermediate progenitor cell identity by attenuating beta-catenin/Armadillo activity. Development 141:51–62PubMedGoogle Scholar
  55. Kraut R, Campos-Ortega JA (1996) inscuteable, a neural precursor gene of Drosophila, encodes a candidate for a cytoskeleton adaptor protein. Dev Biol 174:65–81PubMedGoogle Scholar
  56. Kraut R, Chia W, Jan LY, Jan YN, Knoblich JA (1996) Role of inscuteable in orienting asymmetric cell divisions in Drosophila. Nature 383:50–55PubMedGoogle Scholar
  57. Kumar A, Bello B, Reichert H (2009) Lineage-specific cell death in postembryonic brain development of Drosophila. Development 136:3433–3442PubMedGoogle Scholar
  58. 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 326:224–236PubMedGoogle Scholar
  59. Larsen C, Shy D, Spindler SR, Fung S, Pereanu W, Younossi-Hartenstein A, Hartenstein V (2009) Patterns of growth, axonal extension and axonal arborization of neuronal lineages in the developing Drosophila brain. Dev Biol 335:289–304PubMedCentralPubMedGoogle Scholar
  60. Lee CY, 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 20:3464–3474PubMedCentralPubMedGoogle Scholar
  61. 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 10:441–449PubMedGoogle Scholar
  62. Li L, Vaessin H (2000) Pan-neural Prospero terminates cell proliferation during Drosophila neurogenesis. Genes Dev 14:147–151PubMedCentralPubMedGoogle Scholar
  63. Li S, Wang C, Sandanaraj E, Aw SS, Koe CT, Wong JJ, Yu F, Ang BT, Tang C, Wang H (2014) The SCFSlimb E3 ligase complex regulates asymmetric division to inhibit neuroblast overgrowth. EMBO Rep 15:165–174PubMedGoogle Scholar
  64. Li X, Erclik T, Bertet C, Chen Z, Voutev R, Venkatesh S, Morante J, Celik A, Desplan C (2013) Temporal patterning of Drosophila medulla neuroblasts controls neural fates. Nature 498:456–462PubMedCentralPubMedGoogle Scholar
  65. Lin S, Lai SL, Yu HH, Chihara T, Luo L, Lee T (2010) Lineage-specific effects of Notch/Numb signaling in post-embryonic development of the Drosophila brain. Development 137:43–51PubMedCentralPubMedGoogle Scholar
  66. Lovick JK, Ngo KT, Omoto JJ, Wong DC, Nguyen JD, Hartenstein V (2013) Postembryonic lineages of the Drosophila brain: I. Development of the lineage associated fiber tracts Dev Biol 384:228–257PubMedGoogle Scholar
  67. Maurange C, Cheng L, Gould AP (2008) Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila. Cell 133:891–902PubMedGoogle Scholar
  68. Nakajima A, Isshiki T, Kaneko K, Ishihara S (2010) Robustness under functional constraint: the genetic network for temporal expression in Drosophila neurogenesis. PLoS Comput Biol 6:e1000760PubMedCentralPubMedGoogle Scholar
  69. Neumuller RA, Knoblich JA (2009) Wicked views on stem cell news. Nat Cell Biol 11:678–679PubMedGoogle Scholar
  70. Neumuller RA, Richter C, Fischer A, Novatchkova M, Neumuller KG, Knoblich JA (2011) Genome-wide analysis of self-renewal in Drosophila neural stem cells by transgenic RNAi. Cell Stem Cell 8:580–593PubMedCentralPubMedGoogle Scholar
  71. Novotny T, Eiselt R, Urban J (2002) Hunchback is required for the specification of the early sublineage of neuroblast 7-3 in the Drosophila central nervous system. Development 129:1027–1036PubMedGoogle Scholar
  72. Ohshiro T, Yagami T, Zhang C, Matsuzaki F (2000) Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast. Nature 408:593–596PubMedGoogle Scholar
  73. Overton PM, Meadows LA, Urban J, Russell S (2002) Evidence for differential and redundant function of the Sox genes Dichaete and SoxN during CNS development in Drosophila. Development 129:4219–4228PubMedGoogle Scholar
  74. Pearson BJ, Doe CQ (2003) Regulation of neuroblast competence in Drosophila. Nature 425:624–628PubMedGoogle Scholar
  75. Peng CY, Manning L, Albertson R, Doe CQ (2000) The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts. Nature 408:596–600PubMedGoogle Scholar
  76. Peterson C, Carney GE, Taylor BJ, White K (2002) reaper is required for neuroblast apoptosis during Drosophila development. Development 129:1467–1476PubMedGoogle Scholar
  77. Prokop A, Technau GM (1991) The origin of postembryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster. Development 111:79–88PubMedGoogle Scholar
  78. Randhawa R, Cohen P (2005) The role of the insulin-like growth factor system in prenatal growth. Mol Genet Metab 86:84–90PubMedGoogle Scholar
  79. Reddy BV, Rauskolb C, Irvine KD (2010) Influence of fat-hippo and notch signaling on the proliferation and differentiation of Drosophila optic neuroepithelia. Development 137:2397–2408PubMedCentralPubMedGoogle Scholar
  80. Reichert H (2011) Drosophila neural stem cells: cell cycle control of self-renewal, differentiation, and termination in brain development. Results Probl Cell Differ 53:529–546PubMedGoogle Scholar
  81. 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 76:477–491PubMedGoogle Scholar
  82. Schaefer M, Knoblich JA (2001) Protein localization during asymmetric cell division. Exp Cell Res 271:66–74PubMedGoogle Scholar
  83. Schmidt H, Rickert C, Bossing T, Vef O, Urban J, Technau GM (1997) The embryonic central nervous system lineages of Drosophila melanogaster. II. Neuroblast lineages derived from the dorsal part of the neuroectoderm. Dev Biol 189:186–204PubMedGoogle Scholar
  84. Shen CP, Jan LY, Jan YN (1997) Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila. Cell 90:449–458PubMedGoogle Scholar
  85. Shim J, Gururaja-Rao S, Banerjee U (2013) Nutritional regulation of stem and progenitor cells in Drosophila. Development 140:4647–4656PubMedCentralPubMedGoogle Scholar
  86. 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 20:643–648PubMedCentralPubMedGoogle Scholar
  87. Siller KH, Cabernard C, Doe CQ (2006) The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts. Nat Cell Biol 8:594–600PubMedGoogle Scholar
  88. Skeath JB (1999) At the nexus between pattern formation and cell-type specification: the generation of individual neuroblast fates in the Drosophila embryonic central nervous system. BioEssays 21:922–931PubMedGoogle Scholar
  89. Skeath JB, Thor S (2003) Genetic control of Drosophila nerve cord development. Curr Opin Neurobiol 13:8–15PubMedGoogle Scholar
  90. Sousa-Nunes R, Yee LL, Gould AP (2011) Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature 471:508–512PubMedCentralPubMedGoogle Scholar
  91. Spana EP, Doe CQ (1996) Numb antagonizes Notch signaling to specify sibling neuron cell fates. Neuron 17:21–26PubMedGoogle Scholar
  92. Spana EP, Kopczynski C, Goodman CS, Doe CQ (1995) Asymmetric localization of numb autonomously determines sibling neuron identity in the Drosophila CNS. Development 121:3489–3494PubMedGoogle Scholar
  93. Speicher S, Fischer A, Knoblich J, Carmena A (2008) The PDZ protein Canoe regulates the asymmetric division of Drosophila neuroblasts and muscle progenitors. Curr Biol 18:831–837PubMedGoogle Scholar
  94. Suzuki T, Kaido M, Takayama R, Sato M (2013) A temporal mechanism that produces neuronal diversity in the Drosophila visual center. Dev Biol 380:12–24PubMedGoogle Scholar
  95. Technau GM, Berger C, Urbach R (2006) Generation of cell diversity and segmental pattern in the embryonic central nervous system of Drosophila. Dev Dyn 235:861–869PubMedGoogle Scholar
  96. Touma JJ, Weckerle FF, Cleary MD (2012) Drosophila Polycomb complexes restrict neuroblast competence to generate motoneurons. Development 139:657–666PubMedGoogle Scholar
  97. Tran KD, Doe CQ (2008) Pdm and Castor close successive temporal identity windows in the NB3-1 lineage. Development 135:3491–3499PubMedCentralPubMedGoogle Scholar
  98. Truman JW, Bate M (1988) Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster. Dev Biol 125:145–157PubMedGoogle Scholar
  99. Truman JW, Moats W, Altman J, Marin EC, Williams DW (2010) Role of Notch signaling in establishing the hemilineages of secondary neurons in Drosophila melanogaster. Development 137:53–61PubMedCentralPubMedGoogle Scholar
  100. 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 135:3859–3869PubMedGoogle Scholar
  101. 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 58:349–360PubMedGoogle Scholar
  102. Urbach R, Technau GM (2003) Molecular markers for identified neuroblasts in the developing brain of Drosophila. Development 130:3621–3637PubMedGoogle Scholar
  103. Urbach R, Technau GM (2004) Neuroblast formation and patterning during early brain development in Drosophila. BioEssays 26:739–751PubMedGoogle Scholar
  104. Viktorin G, Riebli N, Popkova A, Giangrande A, Reichert H (2011) Multipotent neural stem cells generate glial cells of the central complex through transit amplifying intermediate progenitors in Drosophila brain development. Dev Biol 356:553–565PubMedGoogle Scholar
  105. Viktorin G, Riebli N, Reichert H (2013) A multipotent transit-amplifying neuroblast lineage in the central brain gives rise to optic lobe glial cells in Drosophila. Dev Biol 379:182–194PubMedGoogle Scholar
  106. Wang H, Cai Y, Chia W, Yang X (2006a) Drosophila homologs of mammalian TNF/TNFR-related molecules regulate segregation of Miranda/Prospero in neuroblasts. EMBO J 25:5783–5793PubMedCentralPubMedGoogle Scholar
  107. Wang H, Ouyang Y, Somers WG, Chia W, Lu B (2007) Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon. Nature 449:96–100PubMedCentralPubMedGoogle Scholar
  108. Wang H, Somers GW, Bashirullah A, Heberlein U, Yu F, Chia W (2006b) Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Genes Dev 20:3453–3463PubMedCentralPubMedGoogle Scholar
  109. Weng M, Golden KL, Lee CY (2010) dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila. Dev Cell 18:126–135PubMedGoogle Scholar
  110. Weng M, Lee CY (2011) Keeping neural progenitor cells on a short leash during Drosophila neurogenesis. Curr Opin Neurobiol 21:36–42PubMedCentralPubMedGoogle Scholar
  111. 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 135:161–173PubMedCentralPubMedGoogle Scholar
  112. Wu PS, Egger B, Brand AH (2008) Asymmetric stem cell division: lessons from Drosophila. Semin Cell Dev Biol 19:283–293PubMedGoogle Scholar
  113. Xiao Q, Komori H, Lee CY (2012) klumpfuss distinguishes stem cells from progenitor cells during asymmetric neuroblast division. Development 139:2670–2680PubMedCentralPubMedGoogle Scholar
  114. Yamanaka T, Horikoshi Y, Izumi N, Suzuki A, Mizuno K, Ohno S (2006) Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity. J Cell Sci 119:2107–2118PubMedGoogle Scholar
  115. Yasugi S, Mizuno T (2008) Molecular analysis of endoderm regionalization. Dev Growth Differ 50(Suppl 1):S79–96Google Scholar
  116. 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 135:1471–1480PubMedGoogle Scholar
  117. Younossi-Hartenstein A, Nassif C, Green P, Hartenstein V (1996) Early neurogenesis of the Drosophila brain. J Comp Neurol 370:313–329PubMedGoogle Scholar
  118. Zhong W, Chia W (2008) Neurogenesis and asymmetric cell division. Curr Opin Neurobiol 18:4–11PubMedGoogle Scholar
  119. Zhong W, Feder JN, Jiang MM, Jan LY, Jan YN (1996) Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis. Neuron 17:43–53PubMedGoogle Scholar
  120. Zhu S, Lin S, Kao CF, Awasaki T, Chiang AS, Lee T (2006) Gradients of the Drosophila Chinmo BTB-zinc finger protein govern neuronal temporal identity. Cell 127:409–422PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.KAIST Institute of BioCenturyKorea Advanced Institute of Science and TechnologyDaejeonSouth Korea
  2. 2.Biozentrum, University of BaselKlingelbergstrasse 50/70BaselSwitzerland

Personalised recommendations