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Neural Stem Cells and Brain Tumour Models in Drosophila

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Neurogenetics

Part of the book series: Learning Materials in Biosciences ((LMB))

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Abstract

During development organs and tissues grow in size. This growth can be achieved either by increasing the size of individual cells or by increasing the number of cells by cell proliferation. In an organ like the brain, it is crucial to control the number of cells in order to build functional neuronal circuits. In this chapter, we will look at different types of neural precursor cells in the growing Drosophila larval brain. Each type of neural precursor cell type in Drosophila displays a rather stereotype division pattern. Different modes of division serve to either expand or to differentiate the precursor cell pool. We will learn that different division modes will lead to vastly different outcomes in terms of the generated cell lineage size. The different neural precursor types use also different timings and cellular mechanisms to terminate proliferation once the correct number of progeny cells is reached.

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References

  1. Gateff E. Malignant neoplasms of genetic origin in Drosophila melanogaster. Science. 1978;200(4349):1448–59.

    Article  CAS  Google Scholar 

  2. Miles WO, Dyson NJ, Walker JA. Modeling tumor invasion and metastasis in Drosophila. Dis Model Mech. 2011;4(6):753–61.

    Article  CAS  Google Scholar 

  3. Knoblich JA. Asymmetric cell division: recent developments and their implications for tumour biology. Nat Rev Mol Cell Biol. 2010;11(12):849–60.

    Article  CAS  Google Scholar 

  4. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  Google Scholar 

  5. Egger B, Chell JM, Brand AH. Insights into neural stem cell biology from flies. Philos Trans R Soc Lond Ser B Biol Sci. 2008;363(1489):39–56.

    Article  CAS  Google Scholar 

  6. Zhang R, Engler A, Taylor V. Notch: an interactive player in neurogenesis and disease. Cell Tissue Res. 2018;371(1):73–89.

    Article  CAS  Google Scholar 

  7. Kaltschmidt JA, Brand AH. Asymmetric cell division: microtubule dynamics and spindle asymmetry. J Cell Sci. 2002;115(Pt 11):2257–64.

    Article  CAS  Google Scholar 

  8. Rebollo E, Roldan M, Gonzalez C. Spindle alignment is achieved without rotation after the first cell cycle in Drosophila embryonic neuroblasts. Development. 2009;136(20):3393–7.

    Article  CAS  Google Scholar 

  9. Doe CQ. Neural stem cells: balancing self-renewal with differentiation. Development. 2008;135(9):1575–87.

    Article  CAS  Google Scholar 

  10. Choksi SP, Southall TD, Bossing T, Edoff K, de Wit E, Fischer BE, et al. Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Dev Cell. 2006;11(6):775–89.

    Article  CAS  Google Scholar 

  11. Siegrist SE, Doe CQ. Extrinsic cues orient the cell division axis in Drosophila embryonic neuroblasts. Development. 2006;133(3):529–36.

    Article  CAS  Google Scholar 

  12. Yoshiura S, Ohta N, Matsuzaki F. Tre1 GPCR signaling orients stem cell divisions in the Drosophila central nervous system. Dev Cell. 2012;22(1):79–91.

    Article  CAS  Google Scholar 

  13. Maurange C, Gould AP. Brainy but not too brainy: starting and stopping neuroblast divisions in Drosophila. Trends Neurosci. 2005;28(1):30–6.

    Article  CAS  Google Scholar 

  14. Sousa-Nunes R, Cheng LY, Gould AP. Regulating neural proliferation in the Drosophila CNS. Curr Opin Neurobiol. 2010;20(1):50–7.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  16. Chell JM, Brand AH. Nutrition-responsive glia control exit of neural stem cells from quiescence. Cell. 2010;143(7):1161–73.

    Article  CAS  Google Scholar 

  17. Sousa-Nunes R, Yee LL, Gould AP. Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature. 2011;471(7339):508–12.

    Article  CAS  Google Scholar 

  18. Bello BC, Hirth F, Gould AP. A pulse of the Drosophila Hox protein Abdominal-A schedules the end of neural proliferation via neuroblast apoptosis. Neuron. 2003;37(2):209–19.

    Article  CAS  Google Scholar 

  19. Homem CC, Steinmann V, Burkard TR, Jais A, Esterbauer H, Knoblich JA. Ecdysone and mediator change energy metabolism to terminate proliferation in Drosophila neural stem cells. Cell. 2014;158(4):874–88.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. Boone JQ, Doe CQ. Identification of Drosophila type II neuroblast lineages containing transit amplifying ganglion mother cells. Dev Neurobiol. 2008;68(9):1185–95.

    Article  Google Scholar 

  22. Bowman SK, Rolland V, Betschinger J, Kinsey KA, Emery G, Knoblich JA. The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev Cell. 2008;14(4):535–46.

    Article  CAS  Google Scholar 

  23. Bello BC, Izergina N, Caussinus E, Reichert H. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development. Neural Develop. 2008;3:5.

    Article  Google Scholar 

  24. Siegrist SE. Termination of Drosophila mushroom body neurogenesis via autophagy and apoptosis. Autophagy. 2019;15(8):1481–2.

    Article  Google Scholar 

  25. Green P, Hartenstein AY, Hartenstein V. The embryonic development of the Drosophila visual system. Cell Tissue Res. 1993;273(3):583–98.

    Article  CAS  Google Scholar 

  26. Hofbauer A, Campos-Ortega JA. Proliferation pattern and early differentiation of the optic lobes in Drosophila melanogaster. Rouxs Arch Dev Biol. 1990;198:264–74.

    Article  Google Scholar 

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

    Article  Google Scholar 

  28. Yasugi T, Umetsu D, Murakami S, Sato M, Tabata T. Drosophila optic lobe neuroblasts triggered by a wave of proneural gene expression that is negatively regulated by JAK/STAT. Development. 2008;135(8):1471–80.

    Article  CAS  Google Scholar 

  29. Lanet E, Gould AP, Maurange C. Protection of neuronal diversity at the expense of neuronal numbers during nutrient restriction in the Drosophila visual system. Cell Rep. 2013;3(3):587–94.

    Article  CAS  Google Scholar 

  30. Wu JS, Luo L. A protocol for mosaic analysis with a repressible cell marker (MARCM) in Drosophila. Nat Protoc. 2006;1(6):2583–9.

    Article  CAS  Google Scholar 

  31. Lee T, Luo L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron. 1999;22(3):451–61.

    Article  CAS  Google Scholar 

  32. Gonzalez C. Spindle orientation, asymmetric division and tumour suppression in Drosophila stem cells. Nat Rev. 2007;8(6):462–72.

    Article  CAS  Google Scholar 

  33. Janssens DH, Lee CY. It takes two to tango, a dance between the cells of origin and cancer stem cells in the Drosophila larval brain. Semin Cell Dev Biol. 2014;28:63–9.

    Article  CAS  Google Scholar 

  34. Spana EP, Doe CQ. The Prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila. Development. 1995;121(10):3187–95.

    Article  CAS  Google Scholar 

  35. Matsuzaki F, Ohshiro T, Ikeshima-Kataoka H, Izumi H. Miranda localizes Staufen and Prospero asymmetrically in mitotic neuroblasts and epithelial cells in early Drosophila embryogenesis. Development. 1998;125(20):4089–98.

    Article  CAS  Google Scholar 

  36. Dyer MA, Livesey FJ, Cepko CL, Oliver G. Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nat Genet. 2003;34(1):53–8.

    Article  CAS  Google Scholar 

  37. Betschinger J, Mechtler K, Knoblich JA. Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell. 2006;124(6):1241–53.

    Article  CAS  Google Scholar 

  38. Bello B, Reichert H, Hirth F. The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila. Development. 2006;133(14):2639–48.

    Article  CAS  Google Scholar 

  39. Reichardt I, Bonnay F, Steinmann V, Loedige I, Burkard TR, Meister G, et al. The tumor suppressor Brat controls neuronal stem cell lineages by inhibiting Deadpan and Zelda. EMBO Rep. 2018;19(1):102–17.

    Article  CAS  Google Scholar 

  40. Knoblich JA, Jan LY, Jan YN. Asymmetric segregation of Numb and Prospero during cell division. Nature. 1995;377(6550):624–7.

    Article  CAS  Google Scholar 

  41. Spana EP, Doe CQ. Numb antagonizes Notch signaling to specify sibling neuron cell fates. Neuron. 1996;17(1):21–6.

    Article  CAS  Google Scholar 

  42. Lee CY, Robinson KJ, Doe CQ. Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation. Nature. 2006;439(7076):594–8.

    Article  CAS  Google Scholar 

  43. Song Y, Lu B. Regulation of cell growth by Notch signaling and its differential requirement in normal vs. tumor-forming stem cells in Drosophila. Genes Dev. 2011;25(24):2644–58.

    Article  CAS  Google Scholar 

  44. San-Juan BP, Baonza A. The bHLH factor deadpan is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila. Dev Biol. 2011;352(1):70–82.

    Article  CAS  Google Scholar 

  45. Magadi SS, Voutyraki C, Anagnostopoulos G, Zacharioudaki E, Poutakidou IK, Efraimoglou C, et al. Dissecting Hes-centred transcriptional networks in neural stem cell maintenance and tumorigenesis in Drosophila. Development. 2020;147(22)

    Google Scholar 

  46. Cabernard C, Doe CQ. Apical/basal spindle orientation is required for neuroblast homeostasis and neuronal differentiation in Drosophila. Dev Cell. 2009;17(1):134–41.

    Article  CAS  Google Scholar 

  47. Wismar J, Loffler T, Habtemichael N, Vef O, Geissen M, Zirwes R, et al. The Drosophila melanogaster tumor suppressor gene lethal(3)malignant brain tumor encodes a proline-rich protein with a novel zinc finger. Mech Dev. 1995;53(1):141–54.

    Article  CAS  Google Scholar 

  48. Richter C, Oktaba K, Steinmann J, Muller J, Knoblich JA. The tumour suppressor L(3)mbt inhibits neuroepithelial proliferation and acts on insulator elements. Nat Cell Biol. 2011;13(9):1029–39.

    Article  CAS  Google Scholar 

  49. Stefanatos RK, Vidal M. Tumor invasion and metastasis in Drosophila: a bold past, a bright future. J Genet Genomics. 2011;38(10):431–8.

    Article  CAS  Google Scholar 

  50. Pagliarini RA, Xu T. A genetic screen in Drosophila for metastatic behavior. Science. 2003;302(5648):1227–31.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biology, University of Fribourg, Fribourg, Switzerland

    Boris Egger

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  1. Boris Egger
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Correspondence to Boris Egger .

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  1. Department of Biology, University of Fribourg, Fribourg, Switzerland

    Boris Egger

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Egger, B. (2023). Neural Stem Cells and Brain Tumour Models in Drosophila . In: Egger, B. (eds) Neurogenetics . Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-031-07793-7_5

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