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Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster

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Abstract

Groundbreaking work by Obaid Siddiqi has contributed to the powerful genetic toolkit that is now available for studying the nervous system of Drosophila. Studies carried out in this powerful neurogenetic model system during the last decade now provide insight into the molecular mechanisms that operate in neural stem cells during normal brain development and during abnormal brain tumorigenesis. These studies also provide strong support for the notion that conserved molecular genetic programs act in brain development and disease in insects and mammals including humans.

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References

  • Acampora D, Avantaggiato V, Tuorto F, Barone P, Reichert H, Finkelstein R and Simeone A 1998 Murine Otx1 and Drosophila otd genes share conserved genetic functions required in invertebrate and vertebrate brain development. Dev. 125 1691–1702

    CAS  Google Scholar 

  • Acampora D, Boyl PP, Signore M, Martinez-Barbera JP, Ilengo C, Puelles E, Annino A, Reichert H, Corte G and Simeone A 2001 OTD/OTX2 functional equivalence depends on 5' and 3' UTR-mediated control of Otx2 mRNA for nucleo-cytoplasmic export and epiblast-restricted translation. Dev. 128 4801–4813

    CAS  Google Scholar 

  • 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. Dev. 5 26

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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. Dev. 3 5

    Article  PubMed Central  PubMed  Google Scholar 

  • Berger C, Harzer H, Burkard TR, Steinmann J, van der Horst S, Laurenson AS, Novatchkova M, Reichert H, et al. 2012 FACS purification and transcriptome analysis of Drosophila neural stem cells reveals a role for Klumpfuss in self-renewal. Cell Rep. 2 407–418

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Brand AH and Livesey FJ 2011 Neural stem cell biology in vertebrates and invertebrates: more alike than different? Neuron 70 719–729

    Article  CAS  PubMed  Google Scholar 

  • Brochtrup A and Hummel T 2011 Olfactory map formation in the Drosophila brain: genetic specificity and neuronal variability. Curr. Opin. Neurobiol. 21 85–92

    Article  CAS  PubMed  Google Scholar 

  • Cajal S and Sanchez D 1915 Contribución al conocimiento de los centros nerviosos de los insectos. Trab. Lab. Inv. Biol. 13 1–68

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Darwin C 1871 The descent of man, and selection in relation to sex (John Murray: London)

    Book  Google Scholar 

  • Das A, Chiang A, Davla S, Priya R, Reichert H, Vijayraghavan K and Rodrigues V 2011 Identification and analysis of a glutamatergic local interneuron lineage in the adult Drosophila olfactory system. Neural. Syst. Circuits 1 4

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Egger B, Chell JM and Brand A 2008 Insights into neural stem cell biology from flies. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 363 39–56

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Fietz SA and Huttner WB 2011 Cortical progenitor expansion, self-renewal and neurogenesis-a polarized perspective. Curr. Opin. Neurobiol. 21 23–35

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez C 2013 Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics. Nat. Rev. Cancer. 13 172–183

  • Hartenstein V and Wodarz A 2013 Initial neurogenesis in Drosophila. Wiley. Interdiscip. Rev. Dev. Biol. 2 701–721

    Article  CAS  PubMed  Google Scholar 

  • Homem CC and Knoblich JA 2012 Drosophila neuroblasts: a model for stem cell biology. Dev. 139 4297–4310

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Ito K and Awasaki T 2008 Clonal unit architecture of the adult fly brain. Adv. Exp. Med. Biol. 628 137–158

    Article  CAS  PubMed  Google Scholar 

  • Ito M, Masuda N, Shinomiya K, Endo K and Ito K 2013 Systematic analysis of neural projections reveals clonal composition of the Drosophila brain. Curr. Biol. 23 644–655

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Jiang Y and Reichert H 2012 Programmed cell death in type II neuroblast lineages is required for central complex development in the Drosophila brain. Neural Dev. 7 3

    Article  PubMed Central  PubMed  Google Scholar 

  • Karcavich RE 2005 Generating neuronal diversity in the Drosophila central nervous system: a view from the ganglion mother cells. Dev. Dyn. 232 609–616

    Article  CAS  PubMed  Google Scholar 

  • Karcavich R and 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. 481 240–251

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Knoblich JA 2010 Asymmetric cell division: recent developments and their implications for tumour biology. Nat. Rev. Mol. Cell. Biol. 11 849–860

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kreso A and Dick JE 2014 Evolution of the Cancer Stem Cell Model. Cell Stem Cell 14 275–291.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Lee T and Luo L 1999 Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 22 451–461

    Article  CAS  PubMed  Google Scholar 

  • Leuzinger S, Hirth F, Gerlich D, Acampora D, Simeone A, Gehring WJ, Finkelstein R, Furukubo-Tokunaga K, et al. 1998 Equivalence of the fly orthodenticle gene and the human OTX genes in embryonic brain development of Drosophila. Dev. 125 1703–1710

    CAS  Google Scholar 

  • Li X, Chen Z and Desplan C 2013 Temporal patterning of neural progenitors in Drosophila. Curr. Top. Dev. Biol. 105 69–96

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lichtneckert R and Reichert H 2005 Insights into the urbilaterian brain: conserved genetic patterning mechanisms in insect and vertebrate brain development. Heredity 94 465–477

    Article  CAS  PubMed  Google Scholar 

  • Lichtneckert R and Reichert H 2008 Anteroposterior regionalization of the brain: genetic and comparative aspects. Adv. Exp. Med. Biol. 628 32–41

    Article  PubMed  Google Scholar 

  • Lin S, Lai SL, Yu HH, Chihara T, Luo L and Lee T 2010 Lineage-specific effects of Notch/Numb signaling in post-embryonic development of the Drosophila brain. Dev. 137 43–51

    Article  CAS  Google Scholar 

  • Lui JH, Hansen DV and Kriegstein AR 2011 Development and evolution of the human neocortex. Cell 146 18–36

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maurange C 2012 Temporl specification of neural stem cells: insights from Drosophila neuroblasts. Curr. Top. Dev. Biol. 98 199–228

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

  • Reichert H 2009 Evolutionary conservation of mechanisms for neural regionalization, proliferation and interconnection in brain development. Biol. Lett. 5 112–116

    Article  PubMed Central  PubMed  Google Scholar 

  • Reichert H 2011 Drosophila neural stem cells: cell cycle control of self-renewal, differentiation, and termination in brain development. Results Probl. Cell. Differ. 53 529-546

    Article  CAS  PubMed  Google Scholar 

  • Reichert H and Simeone A 2001 Developmental genetic evidence for a monophyletic origin of the bilaterian brain. Philos. Trans. R. Soc. Lond. B Biol. Sci. 356 1533–1544

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Reya T, Morrison SJ, Clarke MF and Weissman I 2001 Stem cells, cancer, and cancer stem cells. Nature 414 105–111

    Article  CAS  PubMed  Google Scholar 

  • Riebli N, Viktorin G and Reichert H 2013 Early-born neurons in type II neuroblast lineages establish a larval primordium and integrate into adult circuitry during central complex development in Drosophila. Neural Dev. 8 6

    Article  PubMed Central  PubMed  Google Scholar 

  • Rodrigues V and Hummel T 2008 Development of the Drosophila olfactory system. Adv. Exp. Med. Biol. 628 82–101

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Technau GM, Berger C and Urbach R 2006 Generation of cell diversity and segmental pattern in the embryonic central nervous system of Drosophila. Dev. Dyn. 235 861–869

    Article  CAS  PubMed  Google Scholar 

  • Truman JW, Moats W, Altman J, Marin EC and Williams DW 2010 Role of Notch signaling in establishing the hemilineages of secondary neurons in Drosophila melanogaster. Dev. 137 53–61

    Article  CAS  Google Scholar 

  • Urbach R and Technau GM 2004 Neuroblast formation and patterning during early brain development in Drosophila. Bioessays 26 739–751

    Article  CAS  PubMed  Google Scholar 

  • Viktorin G, Riebli N, Popkova A, Giangrande A and 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. 356 553–565

    Article  CAS  PubMed  Google Scholar 

  • Viktorin, Riebli N and Reichert H 2013 A multipotent transit-amplifying neuroblast lineage in the central brain gives rise to optic lobe glial cells in Drosophila. Dev. Biol. 379 182–194

    Article  CAS  PubMed  Google Scholar 

  • Wang YC, Yang JS, Johnston R, Ren Q, Lee YJ, Luan H, Brody T, Odenwald WF and Lee T 2014 Drosophila intermediate neural progenitors produce lineage-dependent related series of diverse neurons. Dev. 141 253–258

    Article  CAS  Google Scholar 

  • Weng M and Lee CY 2011 Keeping neural progenitor cells on a short leash during Drosophila neurogenesis. Curr. Opin. Neurobiol. 21 36–42

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson RI 2013 Early olfactory processing in Drosophila: mechanisms and principles. Annu. Rev. Neurosci. 36 217–241

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wong DC, Lovick JK, Ngo KT, Borisuthirattana W, Omoto JJ and Hartenstein V 2013 Postembryonic lineages of the Drosophila brain: II. Identification of lineage projection patterns based on MARCM clones. Dev. Biol. 384 258–289

    Article  CAS  PubMed  Google Scholar 

  • Yang JS, Awasaki T, Yu HH, He Y, Ding P, Kao JC and Lee T 2013 Diverse neuronal lineages make stereotyped contributions to the Drosophila locomotor control center, the central complex. J. Comp. Neurol. 521 2645–2662

    Article  PubMed Central  PubMed  Google Scholar 

  • Yu HH, Awasaki T, Schroeder MD, Long F, Yang JS, He Y, Ding P, et al. 2013 Clonal development and organization of the adult Drosophila central brain. Curr. Biol. 23 633–643

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgements

The author acknowledges the support of the Swiss NSF.

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Correspondence to Heinrich Reichert.

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[Reichert H 2014 Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster. J. Biosci. 39 1–9] DOI 10.1007/s12038-014-9444-x

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Reichert, H. Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster . J Biosci 39, 595–603 (2014). https://doi.org/10.1007/s12038-014-9444-x

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