Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future

Abstract

Discoveries in fruit flies have greatly contributed to our understanding of neuroscience. The use of an unparalleled wealth of tools, many of which originated between 1910–1960, has enabled milestone discoveries in nervous system development and function. Such findings have triggered and guided many research efforts in vertebrate neuroscience. After 100 years, fruit flies continue to be the choice model system for many neuroscientists. The combinational use of powerful research tools will ensure that this model organism will continue to lead to key discoveries that will impact vertebrate neuroscience.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Morgan, T. H. Sex limited inheritance in Drosophila. Science 32, 120–122 (1910).

    CAS  PubMed  Google Scholar 

  2. Sturtevant, A. H. A History of Genetics (Cold Spring Harbor Laboratory Press, New York, 1966).

    Google Scholar 

  3. Morgan, T. H. & Bridges, C. B. Sex-linked inheritance in Drosophila. Carnegie Institute of Washington Publication 237, 1–88 (1916).

    Google Scholar 

  4. Poulson, D. F. Histogenesis, organogenesis and differentiation in the embryo of Drosophila melanogaster. (ed. Demerec, M.) (Hafner Publishing Co Ltd, Wiley, New York, 1950).

    Google Scholar 

  5. Campos-Ortega, J. A. Cellular interactions during early neurogenesis of Drosophila melanogaster. Trends Neurosci. 11, 400–405 (1988).

    CAS  PubMed  Google Scholar 

  6. Wharton, K. A., Johansen, K. M., Xu, T. & Artavanis-Tsakonas, S. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell 43, 567–581 (1985).

    CAS  PubMed  Google Scholar 

  7. Vassin, H., Bremer, K. A., Knust, E. & Campos-Ortega, J. A. The neurogenic gene Delta of Drosophila melanogaster is expressed in neurogenic territories and encodes a putative transmembrane protein with EGF-like repeats. EMBO J. 6, 3431–3440 (1987).

    PubMed  PubMed Central  Google Scholar 

  8. Artavanis-Tsakonas, S., Matsuno, K. & Fortini, M. E. Notch signaling. Science 268, 225–232 (1995).

    CAS  PubMed  Google Scholar 

  9. Artavanis-Tsakonas, S., Rand, M. D. & Lake, R. J. Notch signaling: cell fate control and signal integration in development. Science 284, 770–776 (1999).

    CAS  PubMed  Google Scholar 

  10. Ellisen, L. W. et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66, 649–661 (1991).

    CAS  PubMed  Google Scholar 

  11. Kopan, R. & Ilagan, M. X. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137, 216–233 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Breunig, J. J., Silbereis, J., Vaccarino, F. M., Sestan, N. & Rakic, P. Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus. Proc. Natl Acad. Sci. USA 104, 20558–20563 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Pavlopoulos, E., Anezaki, M. & Skoulakis, E. M. Neuralized is expressed in the alpha/beta lobes of adult Drosophila mushroom bodies and facilitates olfactory long-term memory formation. Proc. Natl Acad. Sci. USA 105, 14674–14679 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Roca, C. & Adams, R. H. Regulation of vascular morphogenesis by Notch signaling. Genes Dev. 21, 2511–2524 (2007).

    CAS  PubMed  Google Scholar 

  15. Weinstein, A. Coincidence of crossing over in Drosophila melanogaster (Ampelophila). Genetics 3, 135–172 (1918).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Bridges, C. B. & Morgan, T. H. The third-chromosome group of mutant characters of Drosophila melanogaster. Carnegie Institute of Washington Publication 327, 1–251 (1923).

    Google Scholar 

  17. Lewis, E. B. A gene complex controlling segmentation in Drosophila. Nature 276, 565–570 (1978).

    CAS  PubMed  Google Scholar 

  18. Sanchez-Herrero, E., Vernos, I., Marco, R. & Morata, G. Genetic organization of Drosophila bithorax complex. Nature 313, 108–113 (1985).

    CAS  PubMed  Google Scholar 

  19. Kaufman, T. C., Lewis, R. & Wakimoto, B. Cytogenetic analysis of chromosome 3 in Drosophila melanogaster: the homoeotic gene complex in polytene chromosome interval 84a-B. Genetics 94, 115–133 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Garber, R. L., Kuroiwa, A. & Gehring, W. J. Genomic and cDNA clones of the homeotic locus Antennapedia in Drosophila. EMBO J. 2, 2027–2036 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. McGinnis, W., Garber, R. L., Wirz, J., Kuroiwa, A. & Gehring, W. J. A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell 37, 403–408 (1984).

    CAS  PubMed  Google Scholar 

  22. Duboule, D. The rise and fall of Hox gene clusters. Development 134, 2549–2560 (2007).

    CAS  PubMed  Google Scholar 

  23. Alexander, T., Nolte, C. & Krumlauf, R. Hox genes and segmentation of the hindbrain and axial skeleton. Annu. Rev. Cell Dev. Biol. 25, 431–456 (2009).

    CAS  PubMed  Google Scholar 

  24. Dasen, J. S. & Jessell, T. M. Hox networks and the origins of motor neuron diversity. Curr. Top. Dev. Biol. 88, 169–200 (2009).

    CAS  PubMed  Google Scholar 

  25. Dupin, E., Creuzet, S. & Le Douarin, N. M. The contribution of the neural crest to the vertebrate body. Adv. Exp. Med. Biol. 589, 96–119 (2006).

    CAS  PubMed  Google Scholar 

  26. Ghysen, A. & Dambly-Chaudiere, C. From DNA to form: the achaete-scute complex. Genes Dev. 2, 495–501 (1988).

    Google Scholar 

  27. Raffel, D. & Muller, H. J. Position effect and gene divisibility considered in connection with three strikingly similar scute mutations. Genetics 25, 541–583 (1940).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Garcia-Bellido, A. & Santamaria, P. Developmental analysis of the Achaete-Scute system of Drosophila melanogaster. Genetics 88, 469–486 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Garcia-Bellido, A. Genetic analysis of the Achaete-Scute system of Drosophila melanogaster. Genetics 91, 491–520 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Campuzano, S. et al. Molecular genetics of the achaete-scute gene complex of D. melanogaster. Cell 40, 327–338 (1985).

    CAS  PubMed  Google Scholar 

  31. Cabrera, C. V., Martinez-Arias, A. & Bate, M. The expression of three members of the achaete-scute gene complex correlates with neuroblast segregation in Drosophila. Cell 50, 425–433 (1987).

    CAS  PubMed  Google Scholar 

  32. Jarman, A. P., Grau, Y., Jan, L. Y. & Jan, Y. N. atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system. Cell 73, 1307–1321 (1993).

    CAS  PubMed  Google Scholar 

  33. Lo, L. C., Johnson, J. E., Wuenschell, C. W., Saito, T. & Anderson, D. J. Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells. Genes Dev. 5, 1524–1537 (1991).

    CAS  PubMed  Google Scholar 

  34. Bermingham, N. A. et al. Math1: an essential gene for the generation of inner ear hair cells. Science 284, 1837–1841 (1999).

    CAS  PubMed  Google Scholar 

  35. Van Keymeulen, A. et al. Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J. Cell Biol. 187, 91–100 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Maricich, S. M. et al. Merkel cells are essential for light-touch responses. Science 324, 1580–1582 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Bertrand, N., Castro, D. S. & Guillemot, F. Proneural genes and the specification of neural cell types. Nature Rev. Neurosci. 3, 517–530 (2002).

    CAS  Google Scholar 

  38. Quan, X. J. & Hassan, B. A. From skin to nerve: flies, vertebrates and the first helix. Cell. Mol. Life Sci. 62, 2036–2049 (2005).

    CAS  PubMed  Google Scholar 

  39. Uemura, T., Shepherd, S., Ackerman, L., Jan, L. Y. & Jan, Y. N. numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos. Cell 58, 349–360 (1989).

    CAS  PubMed  Google Scholar 

  40. Blochlinger, K., Bodmer, R., Jack, J., Jan, L. Y. & Jan, Y. N. Primary structure and expression of a product from cut, a locus involved in specifying sensory organ identity in Drosophila. Nature 333, 629–635 (1988).

    Google Scholar 

  41. Vaessin, H. et al. prospero is expressed in neuronal precursors and encodes a nuclear protein that is involved in the control of axonal outgrowth in Drosophila. Cell 67, 941–953 (1991).

    CAS  PubMed  Google Scholar 

  42. Nolo, R., Abbott, L. A. & Bellen, H. J. Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila. Cell 102, 349–362 (2000).

    CAS  PubMed  Google Scholar 

  43. Roegiers, F. & Jan, Y. N. Asymmetric cell division. Curr. Opin. Cell Biol. 16, 195–205 (2004).

    CAS  PubMed  Google Scholar 

  44. Wallis, D. et al. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development 130, 221–232 (2003).

    CAS  PubMed  Google Scholar 

  45. Zhong, W. & Chia, W. Neurogenesis and asymmetric cell division. Curr. Opin. Neurobiol. 18, 4–11 (2008).

    PubMed  Google Scholar 

  46. Nusslein-Volhard, C. & Wieschaus, E. Mutations affecting segment number and polarity in Drosophila. Nature 287, 795–801 (1980).

    CAS  PubMed  Google Scholar 

  47. Lewis, E. B., F. Bacher . Methods of feeding ethyl methane sulfonate (EMS) to Drosophila males. Dros. Inf. Serv. 43, 193 (1968).

    Google Scholar 

  48. Jurgens, G., Wieschaus, E., Nusslein-Volhard, C. & Kluding, H. Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster. Rouxs Arch. Dev. Biol. 193, 283–295 (1984).

    CAS  Google Scholar 

  49. Wieschaus, E., Nüsslein-Volhard, C. & Jürgens, G. Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster. Rouxs Arch. Dev. Biol. 193, 296–307 (1984).

    CAS  Google Scholar 

  50. Ho, K. S. & Scott, M. P. Sonic hedgehog in the nervous system: functions, modifications and mechanisms. Curr. Opin. Neurobiol. 12, 57–63 (2002).

    CAS  PubMed  Google Scholar 

  51. Gaiano, N. Strange bedfellows: Reelin and Notch signaling interact to regulate cell migration in the developing neocortex. Neuron 60, 189–191 (2008).

    CAS  PubMed  Google Scholar 

  52. Charron, F. & Tessier-Lavigne, M. The Hedgehog, TGF-β/BMP and Wnt families of morphogens in axon guidance. Adv. Exp. Med. Biol. 621, 116–133 (2007).

    PubMed  Google Scholar 

  53. Pozniak, C. D. & Pleasure, S. J. A tale of two signals: Wnt and Hedgehog in dentate neurogenesis. Sci. STKE 2006, pe5 (2006).

  54. Seeger, M., Tear, G., Ferres-Marco, D. & Goodman, C. S. Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron 10, 409–426 (1993).

    CAS  PubMed  Google Scholar 

  55. Dickson, B. J. & Gilestro, G. F. Regulation of commissural axon pathfinding by slit and its Robo receptors. Annu. Rev. Cell Dev. Biol. 22, 651–675 (2006).

    CAS  PubMed  Google Scholar 

  56. Kolodkin, A. L., Matthes, D. J. & Goodman, C. S. The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 75, 1389–1399 (1993).

    CAS  PubMed  Google Scholar 

  57. Luo, Y., Raible, D. & Raper, J. A. Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75, 217–227 (1993).

    CAS  PubMed  Google Scholar 

  58. Eichmann, A., Le Noble, F., Autiero, M. & Carmeliet, P. Guidance of vascular and neural network formation. Curr. Opin. Neurobiol. 15, 108–115 (2005).

    CAS  PubMed  Google Scholar 

  59. Benzer, S. Behavioral mutants of Drosophila isolated by countercurrent distribution. Proc. Natl Acad. Sci. USA 58, 1112–1119 (1967).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Konopka, R. J. & Benzer, S. Clock mutants of Drosophila melanogaster. Proc. Natl Acad. Sci. USA 68, 2112–2116 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Bargiello, T. A., Jackson, F. R. & Young, M. W. Restoration of circadian behavioural rhythms by gene transfer in Drosophila. Nature 312, 752–754 (1984).

    CAS  PubMed  Google Scholar 

  62. Reddy, P. et al. Molecular analysis of the period locus in Drosophila melanogaster and identification of a transcript involved in biological rhythms. Cell 38, 701–710 (1984).

    CAS  PubMed  Google Scholar 

  63. Zehring, W. A. et al. P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell 39, 369–376 (1984).

    CAS  PubMed  Google Scholar 

  64. Bargiello, T. A. & Young, M. W. Molecular genetics of a biological clock in Drosophila. Proc. Natl Acad. Sci. USA 81, 2142–2146 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Sun, Z. S. et al. RIGUI, a putative mammalian ortholog of the Drosophila period gene. Cell 90, 1003–1011 (1997).

    CAS  PubMed  Google Scholar 

  66. Sehgal, A., Price, J. L., Man, B. & Young, M. W. Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. Science 263, 1603–1606 (1994).

    CAS  PubMed  Google Scholar 

  67. Vitaterna, M. H. et al. Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 264, 719–725 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. King, D. P. et al. The mouse Clock mutation behaves as an antimorph and maps within the W19H deletion, distal of Kit. Genetics 146, 1049–1060 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Takahashi, J. S., Hong, H. K., Ko, C. H. & McDearmon, E. L. The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nature Rev. Genet. 9, 764–775 (2008).

    CAS  PubMed  Google Scholar 

  70. Quinn, W. G., Harris, W. A. & Benzer, S. Conditioned behavior in Drosophila melanogaster. Proc. Natl Acad. Sci. USA 71, 708–712 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Dudai, Y., Jan, Y. N., Byers, D., Quinn, W. G. & Benzer, S. dunce, a mutant of Drosophila deficient in learning. Proc. Natl Acad. Sci. USA 73, 1684–1688 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Byers, D., Davis, R. L. & Kiger, J. A., Jr. Defect in cyclic AMP phosphodiesterase due to the dunce mutation of learning in Drosophila melanogaster. Nature 289, 79–81 (1981).

    CAS  PubMed  Google Scholar 

  73. Davis, R. L. & Kiger, J. A., Jr. Dunce mutants of Drosophila melanogaster: mutants defective in the cyclic AMP phosphodiesterase enzyme system. J. Cell Biol. 90, 101–107 (1981).

    CAS  PubMed  Google Scholar 

  74. Chen, C. N., Denome, S. & Davis, R. L. Molecular analysis of cDNA clones and the corresponding genomic coding sequences of the Drosophila dunce+ gene, the structural gene for cAMP phosphodiesterase. Proc. Natl Acad. Sci. USA 83, 9313–9317 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Livingstone, M. S., Sziber, P. P. & Quinn, W. G. Loss of calcium/calmodulin responsiveness in adenylate cyclase of rutabaga, a Drosophila learning mutant. Cell 37, 205–215 (1984).

    CAS  PubMed  Google Scholar 

  76. McGuire, S. E., Deshazer, M. & Davis, R. L. Thirty years of olfactory learning and memory research in Drosophila melanogaster. Prog. Neurobiol. 76, 328–347 (2005).

    CAS  PubMed  Google Scholar 

  77. Kandel, E. R. & Schwartz, J. H. Molecular biology of learning: modulation of transmitter release. Science 218, 433–443 (1982).

    CAS  PubMed  Google Scholar 

  78. Alberini, C. M. Genes to remember. J. Exp. Biol. 202, 2887–2891 (1999).

    CAS  PubMed  Google Scholar 

  79. Barco, A., Bailey, C. H. & Kandel, E. R. Common molecular mechanisms in explicit and implicit memory. J. Neurochem. 97, 1520–1533 (2006).

    CAS  PubMed  Google Scholar 

  80. Yu, D., Ponomarev, A. & Davis, R. L. Altered representation of the spatial code for odors after olfactory classical conditioning; memory trace formation by synaptic recruitment. Neuron 42, 437–449 (2004).

    CAS  PubMed  Google Scholar 

  81. Pak, W. L., Grossfield, J. & White, N. V. Nonphototactic mutants in a study of vision of Drosophila. Nature 222, 351–354 (1969).

    CAS  PubMed  Google Scholar 

  82. Pak, W. L., Grossfield, J. & Arnold, K. S. Mutants of the visual pathway of Drosophila melanogaster. Nature 227, 518–520 (1970).

    CAS  PubMed  Google Scholar 

  83. Cosens, D. J. & Manning, A. Abnormal electroretinogram from a Drosophila mutant. Nature 224, 285–287 (1969).

    CAS  PubMed  Google Scholar 

  84. Minke, B., Wu, C. & Pak, W. L. Induction of photoreceptor voltage noise in the dark in Drosophila mutant. Nature 258, 84–87 (1975).

    CAS  PubMed  Google Scholar 

  85. Zuker, C. S. The biology of vision of Drosophila. Proc. Natl Acad. Sci. USA 93, 571–576 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Levis, R., Bingham, P. M. & Rubin, G. M. Physical map of the white locus of Drosophila melanogaster. Proc. Natl Acad. Sci. USA 79, 564–568 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Zipursky, S. L. & Rubin, G. M. Determination of neuronal cell fate: lessons from the R7 neuron of Drosophila. Annu. Rev. Neurosci. 17, 373–397 (1994).

    CAS  PubMed  Google Scholar 

  88. Rubin, G. M. & Spradling, A. C. Genetic transformation of Drosophila with transposable element vectors. Science 218, 348–353 (1982).

    CAS  PubMed  Google Scholar 

  89. Montell, C., Jones, K., Hafen, E. & Rubin, G. Rescue of the Drosophila phototransduction mutation trp by germline transformation. Science 230, 1040–1043 (1985).

    CAS  PubMed  Google Scholar 

  90. Montell, C. Visual transduction in Drosophila. Annu. Rev. Cell Dev. Biol. 15, 231–268 (1999).

    CAS  PubMed  Google Scholar 

  91. Wes, P. D. et al. TRPC1, a human homolog of a Drosophila store-operated channel. Proc. Natl Acad. Sci. USA 92, 9652–9656 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Venkatachalam, K. & Montell, C. TRP channels. Annu. Rev. Biochem. 76, 387–417 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Minke, B. & Cook, B. TRP channel proteins and signal transduction. Physiol. Rev. 82, 429–472 (2002).

    CAS  PubMed  Google Scholar 

  94. Dong, X. P. et al. The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature 455, 992–996 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Landouré, G. et al. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nature Genet. 42, 170–174 (2009).

    PubMed  Google Scholar 

  96. Deng, H. X. et al. Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. Nature Genet. 42, 165–169 (2009).

    PubMed  Google Scholar 

  97. Auer-Grumbach, M. et al. Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C. Nature Genet. 42, 160–164 (2009).

    PubMed  Google Scholar 

  98. Kaplan, W. D. & Trout, W. E., 3rd. The behavior of four neurological mutants of Drosophila. Genetics 61, 399–409 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Jan, L. Y. & Jan, Y. N. Properties of the larval neuromuscular junction in Drosophila melanogaster. J. Physiol. 262, 189–214 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Jan, Y. N., Jan, L. Y. & Dennis, M. J. Two mutations of synaptic transmission in Drosophila. Proc. R. Soc. Lond. B Biol. Sci. 198, 87–108 (1977).

    CAS  PubMed  Google Scholar 

  101. Ganetzky, B. & Wu, C. F. Indirect suppression involving behavioral mutants with altered nerve excitability in Drosophila melanogster. Genetics 100, 597–614 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Wu, C. F., Ganetzky, B., Haugland, F. N. & Liu, A. X. Potassium currents in Drosophila: different components affected by mutations of two genes. Science 220, 1076–1078 (1983).

    CAS  PubMed  Google Scholar 

  103. Baumann, A. et al. Molecular organization of the maternal effect region of the Shaker complex of Drosophila: characterization of an I(A) channel transcript with homology to vertebrate Na channel. EMBO J. 6, 3419–3429 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Kamb, A., Iverson, L. E. & Tanouye, M. A. Molecular characterization of Shaker, a Drosophila gene that encodes a potassium channel. Cell 50, 405–413 (1987).

    CAS  PubMed  Google Scholar 

  105. Papazian, D. M., Schwarz, T. L., Tempel, B. L., Jan, Y. N. & Jan, L. Y. Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from Drosophila. Science 237, 749–753 (1987).

    CAS  PubMed  Google Scholar 

  106. Tempel, B. L., Papazian, D. M., Schwarz, T. L., Jan, Y. N. & Jan, L. Y. Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. Science 237, 770–775 (1987).

    CAS  PubMed  Google Scholar 

  107. Salkoff, L. et al. An essential 'set' of K+ channels conserved in flies, mice and humans. Trends Neurosci. 15, 161–166 (1992).

    CAS  PubMed  Google Scholar 

  108. Ganetzky, B. & Wu, C. F. Neurogenetic analysis of potassium currents in Drosophila: synergistic effects on neuromuscular transmission in double mutants. J. Neurogenet. 1, 17–28 (1983).

    CAS  PubMed  Google Scholar 

  109. Warmke, J., Drysdale, R. & Ganetzky, B. A distinct potassium channel polypeptide encoded by the Drosophila eag locus. Science 252, 1560–1562 (1991).

    CAS  PubMed  Google Scholar 

  110. Warmke, J. W. & Ganetzky, B. A family of potassium channel genes related to eag in Drosophila and mammals. Proc. Natl Acad. Sci. USA 91, 3438–3442 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Curran, M. E. et al. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80, 795–803 (1995).

    CAS  PubMed  Google Scholar 

  112. Jan, L. Y. & Jan, Y. N. Cloned potassium channels from eukaryotes and prokaryotes. Annu. Rev. Neurosci. 20, 91–123 (1997).

    CAS  PubMed  Google Scholar 

  113. Jentsch, T. J. Neuronal KCNQ potassium channels: physiology and role in disease. Nature Rev. Neurosci. 1, 21–30 (2000).

    CAS  Google Scholar 

  114. Featherstone, D. E., Chen, K. & Broadie, K. Harvesting and preparing Drosophila embryos for electrophysiological recording and other procedures. J. Vis. Exp. 20 May 2009 (doi: 10.3791/1347).

  115. Brent, J., Werner, K. & McCabe, B. D. Drosophila larval NMJ immunohistochemistry. J. Vis. Exp. 28 March 2009 (doi: 10.3791/1108).

  116. Bellen, H., Budnik, V. The Neuromuscular Junction (ed. W. Sullivan, M. A.a.R. S. H.) (Cold Spring Harbor Laboratory Press, New York, 2000).

    Google Scholar 

  117. Koh, T. W. et al. Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development. J. Cell Biol. 178, 309–322 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Littleton, J. T., Stern, M., Perin, M. & Bellen, H. J. Calcium dependence of neurotransmitter release and rate of spontaneous vesicle fusions are altered in Drosophila synaptotagmin mutants. Proc. Natl Acad. Sci. USA 91, 10888–10892 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Littleton, J. T., Stern, M., Schulze, K., Perin, M. & Bellen, H. J. Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release. Cell 74, 1125–1134 (1993).

    CAS  PubMed  Google Scholar 

  120. DiAntonio, A., Parfitt, K. D. & Schwarz, T. L. Synaptic transmission persists in synaptotagmin mutants of Drosophila. Cell 73, 1281–1290 (1993).

    CAS  PubMed  Google Scholar 

  121. Poodry, C. A., Hall, L. & Suzuki, D. T. Developmental properties of Shibire: a pleiotropic mutation affecting larval and adult locomotion and development. Dev. Biol. 32, 373–386 (1973).

    CAS  PubMed  Google Scholar 

  122. van der Bliek, A. M. & Meyerowitz, E. M. Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature 351, 411–414 (1991).

    CAS  PubMed  Google Scholar 

  123. Poodry, C. A. & Edgar, L. Reversible alteration in the neuromuscular junctions of Drosophila melanogaster bearing a temperature-sensitive mutation, shibire. J. Cell Biol. 81, 520–527 (1979).

    CAS  PubMed  Google Scholar 

  124. Koenig, J. H., Kosaka, T. & Ikeda, K. The relationship between the number of synaptic vesicles and the amount of transmitter released. J. Neurosci. 9, 1937–1942 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Richmond, J. E. & Broadie, K. S. The synaptic vesicle cycle: exocytosis and endocytosis in Drosophila and C. elegans. Curr. Opin. Neurobiol. 12, 499–507 (2002).

    CAS  PubMed  Google Scholar 

  126. Schwarz, T. L. Transmitter release at the neuromuscular junction. Int. Rev. Neurobiol. 75, 105–144 (2006).

    CAS  PubMed  Google Scholar 

  127. Sudhof, T. C. The synaptic vesicle cycle. Annu. Rev. Neurosci. 27, 509–547 (2004).

    PubMed  Google Scholar 

  128. Bellen, H. J. et al. The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167, 761–781 (2004).

    Google Scholar 

  129. Venken, K. J. & Bellen, H. J. Emerging technologies for gene manipulation in Drosophila melanogaster. Nature Rev. Genet. 6, 167–178 (2005).

    CAS  PubMed  Google Scholar 

  130. Venken, K. J. & Bellen, H. J. Transgenesis upgrades for Drosophila melanogaster. Development 134, 3571–3584 (2007).

    CAS  PubMed  Google Scholar 

  131. Hobert, O. The impact of whole genome sequencing on model system genetics: get ready for the ride. Genetics 184, 317–319 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Rong, Y. S. et al. Targeted mutagenesis by homologous recombination in D. melanogaster. Genes Dev. 16, 1568–1581 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Dietzl, G. et al. A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448, 151–156 (2007).

    CAS  PubMed  Google Scholar 

  134. Ni, J. Q. et al. A Drosophila resource of transgenic RNAi lines for neurogenetics. Genetics 182, 1089–1100 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Venken, K. J., He, Y., Hoskins, R. A. & Bellen, H. J. P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 314, 1747–1751 (2006).

    CAS  PubMed  Google Scholar 

  136. Groth, A. C. & Calos, M. P. Phage integrases: biology and applications. J. Mol. Biol. 335, 667–678 (2004).

    CAS  PubMed  Google Scholar 

  137. Golic, K. G. & Lindquist, S. The FLP recombinase of yeast catalyzes site-specific recombination in the Drosophila genome. Cell 59, 499–509 (1989).

    CAS  PubMed  Google Scholar 

  138. Golic, K. G. Site-specific recombination between homologous chromosomes in Drosophila. Science 252, 958–961 (1991).

    CAS  PubMed  Google Scholar 

  139. Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).

    CAS  PubMed  Google Scholar 

  140. Lee, T. & Luo, L. Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development . Trends Neurosci. 24, 251–254 (2001).

    CAS  PubMed  Google Scholar 

  141. Venken, K. J. et al. Versatile P[acman] BAC libraries for transgenesis studies in Drosophila melanogaster. Nature Methods 6, 431–434 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Broadie, K. & Bate, M. Activity-dependent development of the neuromuscular synapse during Drosophila embryogenesis. Neuron 11, 607–619 (1993).

    CAS  PubMed  Google Scholar 

  143. Broadie, K. in Drosophila Protocols (eds Sullivan, W., Ashburner, M. & Hawley, S.) 273–296 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2000).

    Google Scholar 

  144. Howlett, I. C. & Tanouye, M. A. Neurocircuit assays for seizures in epilepsy mutants of Drosophila. J. Vis. Exp. 15 April 2009 (doi: 10.3791/1121).

  145. Nitz, D. A., van Swinderen, B., Tononi, G. & Greenspan, R. J. Electrophysiological correlates of rest and activity in Drosophila melanogaster. Curr. Biol. 12, 1934–1940 (2002).

    CAS  PubMed  Google Scholar 

  146. Gu, H. et al. Cav2-type calcium channels encoded by cac regulate AP-independent neurotransmitter release at cholinergic synapses in adult Drosophila brain. J. Neurophysiol. 101, 42–53 (2009).

    CAS  PubMed  Google Scholar 

  147. Rohrbough, J. & Broadie, K. Electrophysiological analysis of synaptic transmission in central neurons of Drosophila larvae. J. Neurophysiol. 88, 847–860 (2002).

    PubMed  Google Scholar 

  148. Mamiya, A., Beshel, J., Xu, C. & Zhong, Y. Neural representations of airflow in Drosophila mushroom body. PLoS ONE 3, e4063 (2008).

    PubMed  PubMed Central  Google Scholar 

  149. Pfeiffer, B. D. et al. Tools for neuroanatomy and neurogenetics in Drosophila. Proc. Natl Acad. Sci. USA 105, 9715–9720 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Sweeney, S. T., Broadie, K., Keane, J., Niemann, H. & O'Kane, C. J. Targeted expression of tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects. Neuron 14, 341–351 (1995).

    CAS  PubMed  Google Scholar 

  151. Kitamoto, T. Targeted expression of temperature-sensitive dynamin to study neural mechanisms of complex behavior in Drosophila. J. Neurogenet. 16, 205–228 (2002).

    CAS  PubMed  Google Scholar 

  152. Ren, D. et al. A prokaryotic voltage-gated sodium channel. Science 294, 2372–2375 (2001).

    CAS  PubMed  Google Scholar 

  153. Luan, H. et al. Functional dissection of a neuronal network required for cuticle tanning and wing expansion in Drosophila. J. Neurosci. 26, 573–584 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Miesenbock, G. The optogenetic catechism. Science 326, 395–399 (2009).

    PubMed  Google Scholar 

  155. Shaw, P. J., Cirelli, C., Greenspan, R. J. & Tononi, G. Correlates of sleep and waking in Drosophila melanogaster. Science 287, 1834–1837 (2000).

    CAS  PubMed  Google Scholar 

  156. Harbison, S. T., Mackay, T. F. & Anholt, R. R. Understanding the neurogenetics of sleep: progress from Drosophila. Trends Genet. 25, 262–269 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Cirelli, C. The genetic and molecular regulation of sleep: from fruit flies to humans. Nature Rev. Neurosci. 10, 549–560 (2009).

    CAS  Google Scholar 

  158. Koh, K. et al. Identification of SLEEPLESS, a sleep-promoting factor. Science 321, 372–376 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Wu, M. N. et al. SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker. Nature Neurosci. 13, 69–75 (2010).

    CAS  PubMed  Google Scholar 

  160. Cirelli, C. et al. Reduced sleep in Drosophila Shaker mutants. Nature 434, 1087–1092 (2005).

    CAS  PubMed  Google Scholar 

  161. Axel, R. Scents and sensibility: a molecular logic of olfactory perception (Nobel lecture). Angew. Chem. Int. Ed Engl. 44, 6110–6127 (2005).

    PubMed  Google Scholar 

  162. Anderson, D. J. Profile of David J. Anderson. Interview by Kaspar D. Mossman. Proc. Natl Acad. Sci. USA 106, 17623–17625 (2009).

    PubMed  Google Scholar 

  163. Lozano, A. M., Lang, A. E., Hutchison, W. D. & Dostrovsky, J. O. New developments in understanding the etiology of Parkinson's disease and in its treatment. Curr. Opin. Neurobiol. 8, 783–790 (1998).

    CAS  PubMed  Google Scholar 

  164. Polymeropoulos, M. H. et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045–2047 (1997).

    CAS  PubMed  Google Scholar 

  165. Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605–608 (1998).

    CAS  PubMed  Google Scholar 

  166. Valente, E. M. et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304, 1158–1160 (2004).

    CAS  PubMed  Google Scholar 

  167. Greene, J. C. et al. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc. Natl Acad. Sci. USA 100, 4078–4083 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Pesah, Y. et al. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development 131, 2183–2194 (2004).

    CAS  PubMed  Google Scholar 

  169. Orr, H. T. & Zoghbi, H. Y. Trinucleotide repeat disorders. Annu. Rev. Neurosci. 30, 575–621 (2007).

    CAS  PubMed  Google Scholar 

  170. Lessing, D. & Bonini, N. M. Maintaining the brain: insight into human neurodegeneration from Drosophila melanogaster mutants. Nature Rev. Genet. 10, 359–370 (2009).

    CAS  PubMed  Google Scholar 

  171. Botas, J. Drosophila researchers focus on human disease. Nature Genet. 39, 589–591 (2007).

    CAS  PubMed  Google Scholar 

  172. Vosshall, L. B. & Stocker, R. F. Molecular architecture of smell and taste in Drosophila. Annu. Rev. Neurosci. 30, 505–533 (2007).

    CAS  PubMed  Google Scholar 

  173. Iliadi, K. G. The genetic basis of emotional behavior: has the time come for a Drosophila model? J. Neurogenet. 23, 136–146 (2009).

    CAS  PubMed  Google Scholar 

  174. Kernan, M. J. Mechanotransduction and auditory transduction in Drosophila. Pflugers Arch. 454, 703–720 (2007).

    CAS  PubMed  Google Scholar 

  175. Fotowat, H., Fayyazuddin, A., Bellen, H. J. & Gabbiani, F. A novel neuronal pathway for visually guided escape in Drosophila melanogaster. J. Neurophysiol. 102, 875–885 (2009).

    PubMed  PubMed Central  Google Scholar 

  176. Manoli, D. S., Meissner, G. W. & Baker, B. S. Blueprints for behavior: genetic specification of neural circuitry for innate behaviors. Trends Neurosci. 29, 444–451 (2006).

    CAS  PubMed  Google Scholar 

  177. Dickson, B. J. Wired for sex: the neurobiology of Drosophila mating decisions. Science 322, 904–909 (2008).

    CAS  PubMed  Google Scholar 

  178. Muller, H. J. Genetic variability, twin hybrids and constant hybrids, in a case of balanced lethal factors. Genetics 3, 422–499 (1918).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Muller, H. J. Artificial transmutation of the gene. Science 66, 84–87 (1927).

    CAS  PubMed  Google Scholar 

  180. Bridges, C. B. Salivary chromosome maps with a key to the banding of the chromosomes of Drosophila melanogaster. J. Hered. 26, 60–64 (1935).

    Google Scholar 

  181. Stern, C. Somatic crossing over and segregation in Drosophila melanogaster. Genetics 21, 625–730 (1936).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Fuccillo, M., Joyner, A. L. & Fishell, G. Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development. Nature Rev. Neurosci. 7, 772–783 (2006).

    CAS  Google Scholar 

  183. Kunes, S. Axonal signals in the assembly of neural circuitry. Curr. Opin. Neurobiol. 10, 58–62 (2000).

    CAS  PubMed  Google Scholar 

  184. Doe, C. Q. Neural stem cells: balancing self-renewal with differentiation. Development 135, 1575–1587 (2008).

    CAS  PubMed  Google Scholar 

  185. Ciani, L. & Salinas, P. C. WNTs in the vertebrate nervous system: from patterning to neuronal connectivity. Nature Rev. Neurosci. 6, 351–362 (2005).

    CAS  Google Scholar 

  186. Legent, K. & Treisman, J. E. Wingless signaling in Drosophila eye development. Methods Mol. Biol. 469, 141–161 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Inestrosa, N. C. & Arenas, E. Emerging roles of Wnts in the adult nervous system. Nature Rev. Neurosci. 11, 77–86 (2010).

    CAS  Google Scholar 

  188. Korkut, C. & Budnik, V. WNTs tune up the neuromuscular junction. Nature Rev. Neurosci. 10, 627–634 (2009).

    CAS  Google Scholar 

  189. Liu, A. & Niswander, L. A. Bone morphogenetic protein signalling and vertebrate nervous system development. Nature Rev. Neurosci. 6, 945–954 (2005).

    CAS  Google Scholar 

  190. Kaphingst, K. & Kunes, S. Pattern formation in the visual centers of the Drosophila brain: wingless acts via decapentaplegic to specify the dorsoventral axis. Cell 78, 437–448 (1994).

    CAS  PubMed  Google Scholar 

  191. Yoshida, S. et al. DPP signaling controls development of the lamina glia required for retinal axon targeting in the visual system of Drosophila. Development 132, 4587–4598 (2005).

    CAS  PubMed  Google Scholar 

  192. Parker, L., Ellis, J. E., Nguyen, M. Q. & Arora, K. The divergent TGF-beta ligand Dawdle utilizes an activin pathway to influence axon guidance in Drosophila. Development 133, 4981–4991 (2006).

    CAS  PubMed  Google Scholar 

  193. Serpe, M. & O'Connor, M. B. The metalloprotease tolloid-related and its TGF-b-like substrate Dawdle regulate Drosophila motoneuron axon guidance. Development 133, 4969–4979 (2006).

    CAS  PubMed  Google Scholar 

  194. Keshishian, H. & Kim, Y. S. Orchestrating development and function: retrograde BMP signaling in the Drosophila nervous system. Trends Neurosci. 27, 143–147 (2004).

    CAS  PubMed  Google Scholar 

  195. James, D., Levine, A. J., Besser, D. & Hemmati-Brivanlou, A. TGFb/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132, 1273–1282 (2005).

    CAS  PubMed  Google Scholar 

  196. Ogawa, K. et al. Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells. J. Cell Sci. 120, 55–65 (2007).

    CAS  PubMed  Google Scholar 

  197. Louvi, A. & Artavanis-Tsakonas, S. Notch signalling in vertebrate neural development. Nature Rev. Neurosci. 7, 93–102 (2006).

    CAS  Google Scholar 

  198. Bardin, A. J., Le Borgne, R. & Schweisguth, F. Asymmetric localization and function of cell-fate determinants: a fly's view. Curr. Opin. Neurobiol. 14, 6–14 (2004).

    CAS  PubMed  Google Scholar 

  199. Carthew, R. W. Pattern formation in the Drosophila eye. Curr. Opin. Genet. Dev. 17, 309–313 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  200. Le Gall, M., De Mattei, C. & Giniger, E. Molecular separation of two signaling pathways for the receptor, Notch. Dev. Biol. 313, 556–567 (2008).

    CAS  PubMed  Google Scholar 

  201. de Bivort, B. L., Guo, H. F. & Zhong, Y. Notch signaling is required for activity-dependent synaptic plasticity at the Drosophila neuromuscular junction. J. Neurogenet. 23, 395–404 (2009).

    PubMed  PubMed Central  Google Scholar 

  202. Hou, J., Tamura, T. & Kidokoro, Y. Delayed synaptic transmission in Drosophila cacophony null embryos. J. Neurophysiol. 100, 2833–2842 (2008).

    PubMed  Google Scholar 

  203. Xue, M. et al. Tilting the balance between facilitatory and inhibitory functions of mammalian and Drosophila Complexins orchestrates synaptic vesicle exocytosis. Neuron 64, 367–380 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  204. Bronk, P. et al. The multiple functions of cysteine-string protein analyzed at Drosophila nerve terminals. J. Neurosci. 25, 2204–2214 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  205. Ohyama, T. et al. Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles. J. Cell Biol. 179, 1481–1496 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  206. Schulze, K. L. et al. rop, a Drosophila homolog of yeast Sec1 and vertebrate n-Sec1/Munc-18 proteins, is a negative regulator of neurotransmitter release in vivo. Neuron 13, 1099–1108 (1994).

    CAS  PubMed  Google Scholar 

  207. Ly, C. V., Yao, C. K., Verstreken, P., Ohyama, T. & Bellen, H. J. straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel a1 subunit. J. Cell Biol. 181, 157–170 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  208. Vilinsky, I., Stewart, B. A., Drummond, J., Robinson, I. & Deitcher, D. L. A Drosophila SNAP-25 null mutant reveals context-dependent redundancy with SNAP-24 in neurotransmission. Genetics 162, 259–271 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  209. Broadie, K. et al. Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila. Neuron 15, 663–673 (1995).

    CAS  PubMed  Google Scholar 

  210. Schulze, K. L., Broadie, K., Perin, M. S. & Bellen, H. J. Genetic and electrophysiological studies of Drosophila syntaxin-1A demonstrate its role in nonneuronal secretion and neurotransmission. Cell 80, 311–320 (1995).

    CAS  PubMed  Google Scholar 

  211. Wu, M. N. et al. Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo. Neuron 23, 593–605 (1999).

    CAS  PubMed  Google Scholar 

  212. Aravamudan, B., Fergestad, T., Davis, W. S., Rodesch, C. K. & Broadie, K. Drosophila UNC-13 is essential for synaptic transmission. Nature Neurosci. 2, 965–971 (1999).

    CAS  PubMed  Google Scholar 

  213. Hiesinger, P. R. et al. The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila. Cell 121, 607–620 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  214. Zhang, B. et al. Synaptic vesicle size and number are regulated by a clathrin adaptor protein required for endocytosis. Neuron 21, 1465–1475 (1998).

    CAS  PubMed  Google Scholar 

  215. Kasprowicz, J. et al. Inactivation of clathrin heavy chain inhibits synaptic recycling but allows bulk membrane uptake. J. Cell Biol. 182, 1007–1016 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  216. Heerssen, H., Fetter, R. D. & Davis, G. W. Clathrin dependence of synaptic-vesicle formation at the Drosophila neuromuscular junction. Curr. Biol. 18, 401–409 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  217. Koh, T. W., Verstreken, P. & Bellen, H. J. Dap160/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis. Neuron 43, 193–205 (2004).

    CAS  PubMed  Google Scholar 

  218. Ramaswami, M., Rao, S., van der Bliek, A., Kelly, R. B. & Krishnan, K. S. Genetic studies on dynamin function in Drosophila. J. Neurogenet. 9, 73–87 (1993).

    CAS  PubMed  Google Scholar 

  219. Verstreken, P. et al. Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release. Cell 109, 101–112 (2002).

    CAS  PubMed  Google Scholar 

  220. Yao, C. K. et al. A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis. Cell 138, 947–960 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  221. Phillips, A. M., Ramaswami, M. & Kelly, L. E. Stoned. Traffic 11, 16–24.

  222. Verstreken, P. et al. Synaptojanin is recruited by endophilin to promote synaptic vesicle uncoating. Neuron 40, 733–748 (2003).

    CAS  PubMed  Google Scholar 

  223. Verstreken, P. et al. Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling. Neuron 63, 203–215 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank B. Ganetzky, S. Yamamoto, M. Rasband, N. Giagtzoglou, M. Xue, J. Kiger, H. Dierick, K. Cook, K. Schulze and B. Hassan for reading the manuscript. We apologize to all our colleagues whose work was not cited because of space constraints. HJB is an investigator of the Howard Hughes Medical Institute, HT is supported by the Amyotrophic Lateral Sclerosis Association and CT is supported by a T32 from the National Institute of Neurological Disorders.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hugo J. Bellen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

OMIM

CADASIL

familial advanced sleep phase syndrome

hereditary motor and sensory neuropathy type IIC

LQT syndrome

mucolipidosis type IV disease

Parkinson's disease

FURTHER INFORMATION

Hugo J. Bellen's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bellen, H., Tong, C. & Tsuda, H. 100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future. Nat Rev Neurosci 11, 514–522 (2010). https://doi.org/10.1038/nrn2839

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2839

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing