Summary
The Drosophila model system has been used to study neurodegenerative diseases by expression of human disease genes in transgenic flies. A different approach is to isolate and characterize Drosophila mutants with progressive neurodegeneration to find novel genes required for brain integrity. Mammalian homologues of these genes might be the genetic basis for some of the various progressive neurodegeneration diseases in humans. Here we describe several such mutants. Some of them reveal degeneration in specific parts of the brain while others affect all brain regions. Cell death can occur through apoptosis or necrosis. In one case, mutant flies show abnormal behavior prior to obvious degeneration while most other mutants reveal such defects only in later stages. These mutants offer a new approach to study basic mechanisms of neurodegeneration and for developing fly models for human diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ashburner M (1989) Drosophila: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor
Bellen HJ, O’Kane CJ, Wilson C, Grossniklaus U, Pearson RK, Gehring WJ (1989) Pelement-mediated enhancer detection: a versatile method to study development in Drosophila. Genes Dev 3: 1288–1300
Benzer S (1967) Behavioural mutants of Drosophila isolated by countercurrent distribution. Proc Natl Acad Sci 58: 1112–1119
Buchanan RL, Benzer S (1993) Defective glia in the Drosophila brain degeneration mutant drop-dead. Neuron 10: 839–850
Coombe PE, Heisenberg M (1986) The structural brain mutant Vacuolar medulla of Drosophila melanogaster with specific behavioral defects and cell degeneration in the adult. J Neurogenet 3: 135–158
De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398: 518–522
Deak P, Omar MM, Saunders RD, Pal M, Komonyi O, Szidonya J, Maroy P, Zhang Y, Ashburner M, Benos P, Savakis C, Siden-Kiamos I, Louis C, Bolshakov VN, Kafatos FC, Madueno E, Modolell J, Glover DM (1997) P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: correlation of physical and cytogenetic maps in chromosomal region 86E–87F. Genetics 147:1697–1722
Fernandez-Funez P, Nino-Rosales ML, de Gouyon B, She WC, Luchak JM, Martinez P, Turiegano E, Benito J, Capovilla M, Skinner PJ, McCall A, Canal I, Orr HT, Zoghbi HY, Botas J (2000) Identification of genes that modify ataxin-1-induced neurodegeneration. Nature 408: 101–106
Glynn P (1999) Neuropathy target esterase. Biochem J 344 Pt 3: 625–631
Heisenberg M, Böhl K (1979) Isolation of anatomical brain mutants of Drosophila by histological means. Z Naturforsch 34: 143–147
Hotta Y, Benzer S (1972) Mapping of behaviour in Drosophila mosaics. Nature 240: 527–535
Jackson GR, Salecker I, Dong X, Yao X, Arnheim N, Faber PW, MacDonald ME, Zipursky SL (1998) Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron 21: 633–642
Johnson MK (1982) The target for initiation of delayed neurotoxicity by organophosphorus esters: biochemical studies and toxicological applications. NY Rev Biochem Toxicol 4: 141–212
Kazemi-Esfarjani P, Benzer S (2000) Genetic suppression of polyglutamine toxicity in Drosophila. Science 287: 1837–1840
Kimberly WT, Zheng JB, Guenette SY, Selkoe DJ (2001) The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J Biol Chem 276: 40288–40292
Kretzschmar D, Pflugfelder GO (2002) Glia in development, function, and neurodegeneration of the adult insect brain. Brain Res Bull 57: 121–131
Kretzschmar D, Brunner A, Wiersdorff V, Pflugfelder GO, Heisenberg M, Schneuwly S (1992) Giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster. Embo J 11: 2531–2539
Kretzschmar D, Hasan G, Sharma S, Heisenberg M, Benzer S (1997) The swiss cheese mutant causes glial hyperwrapping and brain degeneration in Drosophila. J Neurosci 17: 7425–7432
Lotti M (1992) The pathogenesis of organophosphate polyneuropathy. Crit Rev Toxicol 21: 465–487
Lush MJ, Li Y, Read DJ, Willis AC, Glynn P (1998) Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man. Biochem J 332: 1–4
Min KT, Benzer S (1997) Spongecake and eggroll: two hereditary diseases in Drosophila resemble patterns of human brain degeneration. Curr Biol 7: 885–888
Min KT, Benzer S (1999) Preventing neurodegeneration in the Drosophila mutant bubblegum. Science 284: 1985–1988
Moser M, Stempfl T, Li Y, Glynn P, Buttner R, Kretzschmar D (2000) Cloning and expression of the murine sws/NTE gene. Mech Dev 90: 279–282
O’Tousa JE (1997) Normal physiology and retinal degeneration in the Drosophila visual system. Prog Retinal Eye Res 16: 691–703
Perutz MF (1996) Glutamine repeats and inherited neurodegenerative diseases: molecular aspects. Curr Opin Struct Biol 6: 848–858
Price DL, Sisodia SS, Borchelt DR (1998) Genetic neurodegenerative diseases: the human illness and transgenic models. Science 282: 1079–1083
Renfranz PJ, Benzer S (1989) Monoclonal antibody probes discriminate early and late mutant defects in development of the Drosophila retina. Dev Biol 136: 411–429
Reynolds ES (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microskopy. J Cell Biol 17: 208–212
Saint Marie RL, Carlson SD (1983a) Glial membrane specializations and the compartmentalization of the lamina ganglionaris of the housefly. J Neurocytol 12: 243–275
Saint Marie RL, Carlson SD (1983b) The fine structure of glia in the lamina ganglionaris of the housefly, Musca domestica. J Neurocytol 12: 213–241
Sayeed O, Benzer S (1996) Behavioral genetics of thermosensation and hygrosensation in Drosophila. Proc Natl Acad Sci USA 93: 6079–6084
Selkoe DJ (1998) The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer’s disease. Trends Cell Biol 8: 447–453
Struhl G, Greenwald I (1999) Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398: 522–525
Warrick JM, Paulson HL, Gray-Board GL, Bui QT, Fischbeck KH, Pittman RN, Bonini NM (1998) Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell 93: 939–949
Warrick JM, Chan HY, Gray-Board GL, Chai Y, Paulson HL, Bonini NM (1999) Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat Genet 23: 425–428
Wilson C, Pearson RK, Bellen HJ, O’Kane CJ, Grossnikiaus U, Gehring WJ (1989) Pelement-mediated enhancer detection: an efficient method for isolating and characterizing developmentally regulated genes in Drosophila. Genes Dev 3: 1301–1313
Ye Y, Lukinova N, Fortini ME (1999) Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants. Nature 398: 525–529
Zars T (2001) Two thermosensors in Drosophila have different behavioral functions. J Comp Physiol 187: 235–242
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer-Verlag Wien
About this paper
Cite this paper
Tschäpe, JA., Bettencourt da Cruz, A., Kretzschmar, D. (2003). Progressive neurodegeneration in Drosophila: a model system. In: Horowski, R., et al. Advances in Research on Neurodegeneration. Journal of Neural Transmission. Supplementa, vol 65. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0643-3_3
Download citation
DOI: https://doi.org/10.1007/978-3-7091-0643-3_3
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-83907-2
Online ISBN: 978-3-7091-0643-3
eBook Packages: Springer Book Archive