Table of Contents Author Guidelines Submit a Manuscript
Stem Cells International
Volume 2012 (2012), Article ID 486169, 10 pages
http://dx.doi.org/10.1155/2012/486169
Review Article

Neural Stem Cells in Drosophila: Molecular Genetic Mechanisms Underlying Normal Neural Proliferation and Abnormal Brain Tumor Formation

Biozentrum, University of Basel, 4056 Basel, Switzerland

Received 23 November 2011; Accepted 31 March 2012

Academic Editor: Mark LaBarge

Copyright © 2012 Nidhi Saini and Heinrich Reichert. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Y. M. Yamashita, D. L. Jones, and M. T. Fuller, “Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome,” Science, vol. 301, no. 5639, pp. 1547–1550, 2003. View at Publisher · View at Google Scholar · View at Scopus
  2. J. Betschinger and J. A. Knoblich, “Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates,” Current Biology, vol. 14, no. 16, pp. R674–R685, 2004. View at Publisher · View at Google Scholar · View at Scopus
  3. T. Lechler and E. Fuchs, “Asymmetric cell divisions promote stratification and differentiation of mammalian skin,” Nature, vol. 437, no. 7056, pp. 275–280, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. C. Q. Doe, “Neural stem cells: balancing self-renewal with differentiation,” Development, vol. 135, no. 9, pp. 1575–1587, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. R. A. Neumüller and J. A. Knoblich, “Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer,” Genes and Development, vol. 23, no. 23, pp. 2675–2699, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. T. D. Southall, B. Egger, K. S. Gold, and A. H. Brand, “Regulation of self-renewal and differentiation in the Drosophila nervous system,” Cold Spring Harbor Symposia on Quantitative Biology, vol. 73, pp. 523–528, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. P. S. Wu, B. Egger, and A. H. Brand, “Asymmetric stem cell division: lessons from Drosophila,” Seminars in Cell and Developmental Biology, vol. 19, no. 3, pp. 283–293, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. V. Hartenstein, E. Rudloff, and J. A. Campos -Ortega, “The pattern of proliferation of the neuroblasts in the wild-type embryo of Drosophila melanogaster,” Roux's Archives of Developmental Biology, vol. 196, no. 8, pp. 473–485, 1987. View at Publisher · View at Google Scholar · View at Scopus
  9. J. W. Truman and M. Bate, “Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster,” Developmental Biology, vol. 125, no. 1, pp. 145–157, 1988. View at Google Scholar · View at Scopus
  10. A. Prokop and G. M. Technau, “The origin of postembryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster,” Development, vol. 111, no. 1, pp. 79–88, 1991. View at Google Scholar · View at Scopus
  11. K. Ito and Y. Hotta, “Proliferation pattern of postembryonic neuroblasts in the brain of Drosophila melanogaster,” Developmental Biology, vol. 149, no. 1, pp. 134–148, 1992. View at Google Scholar · View at Scopus
  12. J. W. Truman, B. J. Taylor, and T. A. Awad, “Formation of the adult nervous system,” in The Development of Drosophila Melanogaster, M. Bate and A. Martinez-Arias, Eds., pp. 1245–1275, Cold Spring Harbor Laboratory Press, Cold Spring Harbour, NY, USA, 1993. View at Google Scholar
  13. R. Urbach and G. M. Technau, “Molecular markers for identified neuroblasts in the developing brain of Drosophila,” Development, vol. 130, no. 16, pp. 3621–3637, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. C. Maurange and A. P. Gould, “Brainy but not too brainy: starting and stopping neuroblast divisions in Drosophila,” Trends in Neurosciences, vol. 28, no. 1, pp. 30–36, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Morante, T. Erclik, and C. Desplan, “Cell migration in Drosophila optic lobe neurons is controlled by eyeless/Pax6,” Development, vol. 138, no. 4, pp. 687–693, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. T. Lee and L. Luo, “Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development,” Trends in Neurosciences, vol. 24, no. 5, pp. 251–254, 2001. View at Publisher · View at Google Scholar · View at Scopus
  17. J. B. Skeath and S. Thor, “Genetic control of Drosophila nerve cord development,” Current Opinion in Neurobiology, vol. 13, no. 1, pp. 8–15, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. A. Wodarz and W. B. Huttner, “Asymmetric cell division during neurogenesis in Drosophila and vertebrates,” Mechanisms of Development, vol. 120, no. 11, pp. 1297–1309, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. A. Hofbauer and J. A. Campos-Ortega, “Proliferation pattern and early differentiation of the optic lobes in Drosophila melanogaster,” Roux's Archives of Developmental Biology, vol. 198, no. 5, pp. 264–274, 1990. View at Google Scholar · View at Scopus
  20. K. Ito, W. Awano, K. Suzuki, Y. Hiromi, and D. Yamamoto, “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, vol. 124, no. 4, pp. 761–771, 1997. View at Google Scholar · View at Scopus
  21. B. Egger, J. Q. Boone, N. R. Stevens, A. H. Brand, and C. Q. Doe, “Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe,” Neural Development, vol. 2, no. 1, article 1, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. B. C. Bello, N. Izergina, E. Caussinus, and H. Reichert, “Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development,” Neural Development, vol. 3, no. 1, article 5, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Q. Boone and C. Q. Doe, “Identification of Drosophila type II neuroblast lineages containing transit amplifying ganglion mother cells,” Developmental Neurobiology, vol. 68, no. 9, pp. 1185–1195, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. S. K. Bowman, V. Rolland, J. Betschinger, K. A. Kinsey, G. Emery, and J. A. Knoblich, “The tumor suppressors brat and numb regulate transit-amplifying neuroblast lineages in Drosophila,” Developmental Cell, vol. 14, no. 4, pp. 535–546, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. O. A. Bayraktar, J. Q. Boone, M. L. Drummond, and C. Q. Doe, “Drosophila type II neuroblast lineages keep Prospero levels low to generate large clones that contribute to the adult brain central complex,” Neural Development, vol. 5, no. 1, article 26, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Weng, K. L. Golden, and C. Y. Lee, “dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila,” Developmental Cell, vol. 18, no. 1, pp. 126–135, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. A. H. Brand and F. J. Livesey, “Neural stem cell viology in vertebrates and invertebrates: more alike than different?” Neuron, vol. 70, no. 4, pp. 719–729, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. B. Egger, K. S. Gold, and A. H. Brand, “Regulating the balance between symmetric and asymmetric stem cell division in the developing brain,” Fly, vol. 5, no. 3, pp. 237–241, 2011. View at Google Scholar
  29. B. Bello, H. Reichert, and F. Hirth, “The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila,” Development, vol. 133, no. 14, pp. 2639–2648, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Betschinger, K. Mechtler, and J. A. Knoblich, “Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells,” Cell, vol. 124, no. 6, pp. 1241–1253, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. S. P. Choksi, T. D. Southall, T. Bossing et al., “Prospero acts as a binary switch between self-renewal and differentiation in Drosophilaneuralstem cells,” Developmental Cell, vol. 11, no. 6, pp. 775–789, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Y. Lee, B. D. Wilkinson, S. E. Siegrist, R. P. Wharton, and C. Q. Doe, “Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal,” Developmental Cell, vol. 10, no. 4, pp. 441–449, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. E. Caussinus and C. Gonzalez, “Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster,” Nature Genetics, vol. 37, no. 10, pp. 1125–1129, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. C. Gonzalez, “Spindle orientation, asymmetric division and tumour suppression in Drosophila stem cells,” Nature Reviews Genetics, vol. 8, no. 6, pp. 462–472, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. K. White and D. R. Kankel, “Patterns of cell division and cell movement in the formation of the imaginal nervous system in Drosophila melanogaster,” Developmental Biology, vol. 65, no. 2, pp. 296–321, 1978. View at Google Scholar · View at Scopus
  36. P. Green, A. Y. Hartenstein, and V. Hartenstein, “The embryonic development of the Drosophila visual system,” Cell and Tissue Research, vol. 273, no. 3, pp. 583–598, 1993. View at Google Scholar · View at Scopus
  37. J. Ceron, C. González, and F. J. Tejedor, “Patterns of cell division and expression of asymmetric cell fate determinants in postembryonic neuroblast lineages of Drosophila,” Developmental Biology, vol. 230, no. 2, pp. 125–138, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. T. Yasugi, D. Umetsu, S. Murakami, M. Sato, and T. Tabata, “Drosophila optic lobe neuroblasts triggered by a wave of proneural gene expression that is negatively regulated by JAK/STAT,” Development, vol. 135, no. 8, pp. 1471–1480, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. C. Y. Lee, K. J. Robinson, and C. Q. Doe, “Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation,” Nature, vol. 439, no. 7076, pp. 594–598, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. J. A. Knoblich, “Asymmetric cell division during animal development,” Nature Reviews Molecular Cell Biology, vol. 2, no. 1, pp. 11–20, 2001. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Glotzer, “Cleavage furrow positioning,” Journal of Cell Biology, vol. 164, no. 3, pp. 347–351, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Schober, M. Schaefer, and J. A. Knoblich, “Bazooka recruits inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts,” Nature, vol. 402, no. 6761, pp. 548–551, 1999. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Wodarz, A. Ramrath, U. Kuchinke, and E. Knust, “Bazooka provides an apical cue for inscuteable localization in Drosophila neuroblasts,” Nature, vol. 402, no. 6761, pp. 544–547, 1999. View at Publisher · View at Google Scholar · View at Scopus
  44. A. Wodarz, A. Ramrath, A. Grimm, and E. Knust, “Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts,” The Journal of Cell Biology, vol. 150, no. 6, pp. 1361–1374, 2000. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Petronczki and J. A. Knoblich, “DmPAR-6 directs epithelial polarity and asymetric cell division of neuroblasts in Drosophila,” Nature Cell Biology, vol. 3, no. 1, pp. 43–49, 2001. View at Publisher · View at Google Scholar · View at Scopus
  46. M. M. Rolls, R. Albertson, H. P. Shih, C. Y. Lee, and C. Q. Doe, “Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia,” Journal of Cell Biology, vol. 163, no. 5, pp. 1089–1098, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. T. Yamanaka, Y. Horikoshi, N. Izumi, A. Suzuki, K. Mizuno, and S. Ohno, “Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity,” Journal of Cell Science, vol. 119, no. 10, pp. 2107–2118, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. S. X. Atwood and K. E. Prehoda, “aPKC phosphorylates miranda to polarize fate determinants during neuroblast asymmetric cell division,” Current Biology, vol. 19, no. 9, pp. 723–729, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Cabernard and C. Q. Doe, “Apical/basal spindle orientation is required for neuroblast homeostasis and neuronal differentiation in Drosophila,” Developmental Cell, vol. 17, no. 1, pp. 134–141, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. R. Kraut and J. A. Campos-Ortega, “inscuteable, a neural precursor gene of Drosophila, encodes a candidate for a cytoskeleton adaptor protein,” Developmental Biology, vol. 174, no. 1, pp. 65–81, 1996. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Kraut, W. Chia, L. Y. Jan, Y. N. Jan, and J. A. Knoblich, “Role of inscuteable in orienting asymmetric cell divisions in Drosophila,” Nature, vol. 383, no. 6595, pp. 50–55, 1996. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Schaefer, M. Petronczki, D. Dorner, M. Forte, and J. A. Knoblich, “Heterotrimeric G proteins direct two modes of asymmetric cell division in the Drosophila nervous system,” Cell, vol. 107, no. 2, pp. 183–194, 2001. View at Publisher · View at Google Scholar · View at Scopus
  53. N. Fuse, K. Hisata, A. L. Katzen, and F. Matsuzaki, “Heterotrimeric G proteins regulate daughter cell size asymmetry in Drosophila neuroblast divisions,” Current Biology, vol. 13, no. 11, pp. 947–954, 2003. View at Publisher · View at Google Scholar · View at Scopus
  54. F. Yu, Y. Cai, R. Kaushik, X. Yang, and W. Chia, “Distinct roles of Gαi and Gβ13F subunits of the heterotrimeric G protein complex in the mediation of Drosophila neuroblast asymmetric divisions,” Journal of Cell Biology, vol. 162, no. 4, pp. 623–633, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. Y. Izumi, N. Ohta, A. Itoh-Furuya, N. Fuse, and F. Matsuzaki, “Differential functions of G protein and Baz-aPKC signaling pathways in Drosophila neuroblast asymmetric division,” Journal of Cell Biology, vol. 164, no. 5, pp. 729–738, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Schaefer, A. Shevchenko, A. Shevchenko, and J. A. Knoblich, “A protein complex containing inscuteable and the Gα-binding protein pins orients asymmetric cell divisions in Drosophila,” Current Biology, vol. 10, no. 7, pp. 353–362, 2000. View at Publisher · View at Google Scholar · View at Scopus
  57. F. Yu, X. Morin, Y. Cai, X. Yang, and W. Chia, “Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization,” Cell, vol. 100, no. 4, pp. 399–409, 2000. View at Google Scholar · View at Scopus
  58. F. Yu, H. Wang, H. Qian et al., “Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions,” Genes and Development, vol. 19, no. 11, pp. 1341–1353, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. S. K. Bowman, R. A. Neumüller, M. Novatchkova, Q. Du, and J. A. Knoblich, “The Drosophila NuMA homolog mud regulates spindle orientation in asymmetric cell division,” Developmental Cell, vol. 10, no. 6, pp. 731–742, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. Y. Izumi, N. Ohta, K. Hisata, T. Raabe, and F. Matsuzaki, “Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization,” Nature Cell Biology, vol. 8, no. 6, pp. 586–593, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. K. H. Siller, C. Cabernard, and C. Q. Doe, “The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts,” Nature Cell Biology, vol. 8, no. 6, pp. 594–600, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. J. A. Kaltschmidt, C. M. Davidson, N. H. Brown, and A. H. Brand, “Rotation and asymmetry of the mitotic spindle direct asymmetric cell division in the developing central nervous system,” Nature Cell Biology, vol. 2, no. 1, pp. 7–12, 2000. View at Publisher · View at Google Scholar · View at Scopus
  63. E. Rebollo, P. Sampaio, J. Januschke, S. Llamazares, H. Varmark, and C. González, “Functionally Unequal Centrosomes Drive Spindle Orientation in Asymmetrically Dividing Drosophila Neural Stem Cells,” Developmental Cell, vol. 12, no. 3, pp. 467–474, 2007. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Cabernard, K. E. Prehoda, and C. Q. Doe, “A spindle-independent cleavage furrow positioning pathway,” Nature, vol. 467, no. 7311, pp. 91–94, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. W. Chia, W. G. Somers, and H. Wang, “Drosophila neuroblast asymmetric divisions: cell cycle regulators, asymmetric protein localization, and tumorigenesis,” Journal of Cell Biology, vol. 180, no. 2, pp. 267–272, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. P. Gönczy, “Mechanisms of asymmetric cell division: flies and worms pave the way,” Nature Reviews Molecular Cell Biology, vol. 9, no. 5, pp. 355–366, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. J. A. Knoblich, “Mechanisms of asymmetric stem cell division,” Cell, vol. 132, no. 4, pp. 583–597, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. M. S. Rhyu, L. Y. Jan, and Y. N. Jan, “Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells,” Cell, vol. 76, no. 3, pp. 477–491, 1994. View at Publisher · View at Google Scholar · View at Scopus
  69. E. P. Spana, C. Kopczynski, C. S. Goodman, and C. Q. Doe, “Asymmetric localization of numb autonomously determines sibling neuron identity in the Drosophila CNS,” Development, vol. 121, no. 11, pp. 3489–3494, 1995. View at Google Scholar · View at Scopus
  70. M. Guo, L. Y. Jan, and Y. N. Jan, “Control of daughter cell fates during asymmetric division: interaction of Numb and Notch,” Neuron, vol. 17, no. 1, pp. 27–41, 1996. View at Publisher · View at Google Scholar · View at Scopus
  71. E. Santolini, C. Puri, A. E. Salcini et al., “Numb is an endocytic protein,” Journal of Cell Biology, vol. 151, no. 6, pp. 1345–1352, 2000. View at Publisher · View at Google Scholar · View at Scopus
  72. D. Berdnik, T. Török, M. González-Gaitán, and J. A. Knoblich, “The endocytic protein α-adaptin is required for numb-mediated asymmetric cell division in Drosophila,” Developmental Cell, vol. 3, no. 2, pp. 221–231, 2002. View at Publisher · View at Google Scholar · View at Scopus
  73. K. M. O'Connor-Giles and J. B. Skeath, “Numb inhibits membrane localization of sanpodo, a four-pass transmembrane protein, to promote asymmetric divisions in Drosophila,” Developmental Cell, vol. 5, no. 2, pp. 231–243, 2003. View at Publisher · View at Google Scholar · View at Scopus
  74. J. Hirata, H. Nakagoshi, Y. Nabeshima, and F. Matsuzaki, “Asymmetric segregation of the homeodomain protein Prospero during Drosophila development,” Nature, vol. 377, no. 6550, pp. 627–630, 1995. View at Google Scholar · View at Scopus
  75. J. A. Knoblich, L. Y. Jan, and Y. N. Jan, “Asymmetric segregation of Numb and Prospero during cell division,” Nature, vol. 377, no. 6550, pp. 624–627, 1995. View at Google Scholar · View at Scopus
  76. E. P. Spana and C. Q. Doe, “The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila,” Development, vol. 121, no. 10, pp. 3187–3195, 1995. View at Google Scholar · View at Scopus
  77. H. Ikeshima-Kataoka, J. B. Skeath, Y. I. Nabeshima, C. Q. Doe, and F. Matsuzaki, “Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions,” Nature, vol. 390, no. 6660, pp. 625–629, 1997. View at Publisher · View at Google Scholar · View at Scopus
  78. F. Matsuzaki, T. Ohshiro, H. Ikeshima-Kataoka, and H. Izumi, “miranda localizes staufen and prospero asymmetrically in mitotic neuroblasts and epithelial cells in early Drosophila embryogenesis,” Development, vol. 125, no. 20, pp. 4089–4098, 1998. View at Google Scholar · View at Scopus
  79. A. J. Schuldt, J. H. J. Adams, C. M. Davidson et al., “Miranda mediates asymmetric protein and RNA localization in the developing nervous system,” Genes and Development, vol. 12, no. 12, pp. 1847–1857, 1998. View at Google Scholar · View at Scopus
  80. J. Sonoda and R. P. Wharton, “Drosophila brain tumor is a translational repressor,” Genes and Development, vol. 15, no. 6, pp. 762–773, 2001. View at Publisher · View at Google Scholar · View at Scopus
  81. R. A. Neumüller, J. Betschinger, A. Fischer et al., “Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage,” Nature, vol. 454, no. 7201, pp. 241–245, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. J. C. Schwamborn, E. Berezikov, and J. A. Knoblich, “The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors,” Cell, vol. 136, no. 5, pp. 913–925, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. B. Egger, K. S. Gold, and A. H. Brand, “Notch regulates the switch from symmetric to asymmetric neural stem cell division in the Drosophila optic lobe,” Development, vol. 137, no. 18, pp. 2981–2987, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. W. Wang, W. Liu, Y. Wang, L. Zhou, X. Tang, and H. Luo, “Notch signaling regulates neuroepithelial stem cell maintenance and neuroblast formation in Drosophila optic lobe development,” Developmental Biology, vol. 350, no. 2, pp. 414–428, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. K. T. Ngo, J. Wang, M. Junker et al., “Concomitant requirement for Notch and Jak/Stat signaling during neuro-epithelial differentiation in the Drosophila optic lobe,” Developmental Biology, vol. 346, no. 2, pp. 284–295, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. B. V. V. G. Reddy, C. Rauskolb, and K. D. Irvine, “Influence of Fat-Hippo and Notch signaling on the proliferation and differentiation of Drosophila optic neuroepithelia,” Development, vol. 137, no. 14, pp. 2397–2408, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. D. Sprinzak, A. Lakhanpal, L. Lebon et al., “Cis-interactions between Notch and Delta generate mutually exclusive signalling states,” Nature, vol. 465, no. 7294, pp. 86–90, 2010. View at Publisher · View at Google Scholar · View at Scopus
  88. T. Yasugi, A. Sugie, D. Umetsu, and T. Tabata, “Coordinated sequential action of EGFR and Notch signaling pathways regulates proneural wave progression in the Drosophila optic lobe,” Development, vol. 137, no. 19, pp. 3193–3203, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. E. Gateff, “Malignant neoplasms of genetic origin in Drosophila melanogaster,” Science, vol. 200, no. 4349, pp. 1448–1459, 1978. View at Google Scholar · View at Scopus
  90. E. Gateff, “Tumor suppressor and overgrowth suppressor genes of Drosophila melanogaster: developmental aspects,” International Journal of Developmental Biology, vol. 38, no. 4, pp. 565–590, 1994. View at Google Scholar · View at Scopus
  91. T. Ohshiro, T. Yagami, C. Zhang, and F. Matsuzaki, “Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast,” Nature, vol. 408, no. 6812, pp. 593–596, 2000. View at Publisher · View at Google Scholar · View at Scopus
  92. C. Y. Peng, L. Manning, R. Albertson, and C. Q. Doe, “The tumour-suppresor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts,” Nature, vol. 408, no. 6812, pp. 596–600, 2000. View at Publisher · View at Google Scholar · View at Scopus
  93. A. Wodarz, “Molecular control of cell polarity and asymmetric cell division in Drosophila neuroblasts,” Current Opinion in Cell Biology, vol. 17, no. 5, pp. 475–481, 2005. View at Publisher · View at Google Scholar · View at Scopus
  94. E. Castellanos, P. Dominguez, and C. Gonzalez, “Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability,” Current Biology, vol. 18, no. 16, pp. 1209–1214, 2008. View at Publisher · View at Google Scholar · View at Scopus
  95. J. L. Boulay, U. Stiefel, E. Taylor, B. Dolder, A. Merlo, and F. Hirth, “Loss of heterozygosity of TRIM3 in malignant gliomas,” BMC Cancer, vol. 9, article 71, 2009. View at Publisher · View at Google Scholar · View at Scopus
  96. S. Pece, M. Serresi, E. Santolini et al., “Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis,” Journal of Cell Biology, vol. 167, no. 2, pp. 215–221, 2004. View at Publisher · View at Google Scholar · View at Scopus
  97. T. V. Petrova, A. Nykänen, C. Norrmén et al., “Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype,” Cancer Cell, vol. 13, no. 5, pp. 407–419, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. E. Gateff, T. Loffler, and J. Wismar, “A temperature-sensitive brain tumor suppressor mutation of Drosophila melanogaster: developmental studies and molecular localization of the gene,” Mechanisms of Development, vol. 41, no. 1, pp. 15–31, 1993. View at Publisher · View at Google Scholar · View at Scopus
  99. A. Janic, L. Mendizabal, S. Llamazares, D. Rossell, and C. Gonzalez, “Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila,” Science, vol. 330, no. 6012, pp. 1824–1827, 2010. View at Publisher · View at Google Scholar · View at Scopus
  100. C. Richter, K. Oktaba, J. Steinmann et al., “The tumour suppressor L(3)mbt inhibits neuroepithelial proliferation and acts on insulator elements,” Nature Cell Biology, vol. 13, no. 9, pp. 1029–1039, 2011. View at Google Scholar
  101. K. Harvey and N. Tapon, “The Salvador-Warts-Hippo pathway—an emerging tumour-suppressor network,” Nature Reviews Cancer, vol. 7, no. 3, pp. 182–191, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. L. J. Saucedo and B. A. Edgar, “Filling out the Hippo pathway,” Nature Reviews Molecular Cell Biology, vol. 8, no. 8, pp. 613–621, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. B. V. V. G. Reddy and K. D. Irvine, “The fat and warts signaling pathways: new insights into their regulation, mechanism and conservation,” Development, vol. 135, no. 17, pp. 2827–2838, 2008. View at Publisher · View at Google Scholar · View at Scopus
  104. C. J. Potter, G. S. Turenchalk, and T. Xu, “Drosophila in cancer researchan expanding role,” Trends in Genetics, vol. 16, no. 1, pp. 33–39, 2000. View at Publisher · View at Google Scholar · View at Scopus
  105. H. Harris, “A long view of fashions in cancer research,” BioEssays, vol. 27, no. 8, pp. 833–838, 2005. View at Publisher · View at Google Scholar · View at Scopus
  106. T. Loop, R. Leemans, U. Stiefel et al., “Transcriptional signature of an adult brain tumor in Drosophila,” BMC Genomics, vol. 5, no. 1, article 24, 2004. View at Publisher · View at Google Scholar · View at Scopus
  107. T. D. Southall and A. H. Brand, “Neural stem cell transcriptional networks highlight genes essential for nervous system development,” The EMBO Journal, vol. 28, no. 24, pp. 3799–3807, 2009. View at Publisher · View at Google Scholar · View at Scopus
  108. G. Dietzl, D. Chen, F. Schnorrer et al., “A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila,” Nature, vol. 448, no. 7150, pp. 151–156, 2007. View at Publisher · View at Google Scholar · View at Scopus
  109. R. A. Neumüller, C. Richter, A. Fischer, M. Novatchkova, K. G. Neumüller, and J. A. Knoblich, “Genome-wide analysis of self-renewal in Drosophila neural stem cells by transgenic RNAi,” Cell Stem Cell, vol. 8, no. 5, pp. 580–593, 2011. View at Publisher · View at Google Scholar · View at Scopus
  110. J. A. Fischer, E. Giniger, T. Maniatis, and M. Ptashne, “GAL4 activates transcription in Drosophila,” Nature, vol. 332, no. 6167, pp. 853–856, 1988. View at Google Scholar · View at Scopus
  111. A. H. Brand and N. Perrimon, “Targeted gene expression as a means of altering cell fates and generating dominant phenotypes,” Development, vol. 118, no. 2, pp. 401–415, 1993. View at Google Scholar · View at Scopus