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  • Review Article
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The art and design of genetic screens: Drosophila melanogaster

Key Points

  • The success of Drosophila melanogaster as a model organism is largely due to the power of forward genetic screens to identify the genes that are involved in a biological process. Although traditional genetic screens, such as zygotic lethal screens, have been useful for identifying the genes that act early in fly development, more sophisticated and versatile screens have been developed.

  • Modifier screens, in which genes are identified by their ability to alter the phenotype of flies that are genetically sensitized for the process of interest, are useful for finding the components of signal-transduction pathways.

  • Clonal screens, in which cells that are homozygous for a mutation of interest can be made in an otherwise heterozygous animal through targeted mitotic recombination (using the Flp/FRT system), allow researchers to identify genes that act in a specific tissue at any stage of development. A modification of this technique, in which clones are made in the germ line, helps to find genes that are maternally supplied to the embryo.

  • Mutant screens do not always identify all of the genes for which loss-of-function mutations give the phenotype of interest, as with genes that have redundant functions. In these cases, the GAL4UAS system can be used to screen for mis- or overexpression phenotypes.

  • The success of a genetic screen depends in large part on its design. As mapping and identifying genes that result from a screen can be very laborious, it is often preferable to sacrifice speed and the number of genes recovered in favour of a phenotype that is directly related to the process of interest.

  • Genetic screens will continue to be useful in years to come, even once all genes have been identified. The functional characterization of genes relies on having allelic variants of each gene, which, for the time being, only genetic screens can provide.

Abstract

The success of Drosophila melanogaster as a model organism is largely due to the power of forward genetic screens to identify the genes that are involved in a biological process. Traditional screens, such as the Nobel-prize-winning screen for embryonic-patterning mutants, can only identify the earliest phenotype of a mutation. This review describes the ingenious approaches that have been devised to circumvent this problem: modifier screens, for example, have been invaluable for elucidating signal-transduction pathways, whereas clonal screens now make it possible to screen for almost any phenotype in any cell at any stage of development.

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Figure 1: Outline of the crossing schemes used in the Heidelberg screen and the first screen for enhancers of sevenless.
Figure 2: Examples of mutant phenotypes from standard F3 screens, and from a screen for enhancers and suppressors of a rough-eye phenotype.
Figure 3: Examples of mutant phenotypes from Flp/FRT screens.
Figure 4: The eyeFLP technique for targeting clones to the eye.

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References

  1. Kohler, R. E. Lords of the Fly: Drosophila Genetics and the Experimental Life Vol. 15 (Univ. Chicago Press, Chicago, Illinois, 1994).

    Google Scholar 

  2. Rubin, G. M. & Lewis, E. B. A brief history of Drosophila's contributions to genome research. Science 287, 2216–2218 (2000).

    CAS  PubMed  Google Scholar 

  3. Holley, S. A. et al. A conserved system for dorsal–ventral patterning in insects and vertebrates involving sog and chordin. Nature 376, 249–253 (1995).

    CAS  PubMed  Google Scholar 

  4. Pearse, R. V. & Tabin, C.J. The molecular ZPA. J. Exp. Zool. 282, 677–690 (1998).

    CAS  PubMed  Google Scholar 

  5. Adams, M. D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).

    PubMed  Google Scholar 

  6. Friedman, R. & Hughes, A. L. Pattern and timing of gene duplication in animal genomes. Genome Res. 11, 1842–1847 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Fortini, M. E., Skupski, M. P., Boguski, M. S. & Hariharan, I. K. A survey of human disease gene counterparts in the Drosophila genome. J. Cell Biol. 150, F23–F30 (2000).

    CAS  PubMed  Google Scholar 

  8. Feany, M. B. & Bender, W. W. A Drosophila model of Parkinson's disease. Nature 404, 394–398 (2000).

    CAS  PubMed  Google Scholar 

  9. Lewis, E. B. & Bacher, F. Methods of feeding ethyl methane sulphonate (EMS) to Drosophila males. Drosoph. Inf. Serv. 43, 193 (1968).

    Google Scholar 

  10. Nüsslein-Volhard, C. & Wieschaus, E. Mutations affecting segment number and polarity in Drosophila. Nature 287, 795–801 (1980).A classic paper describing some of the mutants from the first large-scale screens that set out to saturate the genome for mutations that affect a particular process.

    PubMed  Google Scholar 

  11. Nüsslein-Volhard, C., Wieschaus, E. & Kluding, H. Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster: zygotic loci on the second chromosome. Roux's Arch. Dev. Biol. 193, 267–282 (1984).A more detailed description of the large-scale screens for embryonic patterning mutants; it contains a valuable discussion on how to assess the degree of saturation.

    Google Scholar 

  12. Lawrence, P. A. The Making of the Fly: the Genetics of Animal Design (Blackwell, Oxford, 1992).

  13. Wieschaus, E. Embryonic transcription and the control of developmental pathways. Genetics 142, 5–10 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Nüsslein-Volhard, C., Frohnhöfer, H. G. & Lehmann, R. Determination of anteroposterior polarity in Drosophila. Science 238, 1675–1681 (1987).

    PubMed  Google Scholar 

  15. Schüpbach, T. & Wieschaus, E. Maternal-effect mutations altering the anterior–posterior pattern of the Drosophila embryo. Roux's Arch. Dev. Biol. 195, 302–317 (1986).

    Google Scholar 

  16. 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 

  17. Kolodziej, P. A., Jan, L. Y. & Jan, Y. N. Mutations that affect the length, fasciculation, or ventral orientation of specific sensory axons in the Drosophila embryo. Neuron 15, 273–286 (1995).

    CAS  PubMed  Google Scholar 

  18. Kidd, T. et al. Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 92, 205–215 (1998).

    CAS  PubMed  Google Scholar 

  19. Tear, G. et al. commissureless controls growth cone guidance across the CNS midline in Drosophila and encodes a novel membrane protein. Neuron 16, 501–514 (1996).

    CAS  PubMed  Google Scholar 

  20. Gao, F. B., Brenman, J. E., Jan, L. Y. & Jan, Y. N. Genes regulating dendritic outgrowth, branching, and routing in Drosophila. Genes Dev. 13, 2549–2561 (1999).A recent example of how the traditional screening approach can be combined with sophisticated labelling techniques to find mutants that affect a specific process.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Gao, F. B., Kohwi, M., Brenman, J. E., Jan, L. Y. & Jan, Y. N. Control of dendritic field formation in Drosophila: the roles of flamingo and competition between homologous neurons. Neuron 28, 91–101 (2000).

    CAS  PubMed  Google Scholar 

  22. Brenman, J. E., Gao, F. B., Jan, L. Y. & Jan, Y. N. Sequoia, a tramtrack-related zinc finger protein, functions as a pan-neural regulator for dendrite and axon morphogenesis in Drosophila. Dev. Cell 1, 667–677 (2001).

    CAS  PubMed  Google Scholar 

  23. Muller, H., Samanta, R. & Wieschaus, E. Wingless signaling in the Drosophila embryo: zygotic requirements and the role of the frizzled genes. Development 126, 577–586 (1999).

    CAS  PubMed  Google Scholar 

  24. Brunner, E., Peter, O., Schweizer, L. & Basler, K. pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila. Nature 385, 829–833 (1997).

    CAS  PubMed  Google Scholar 

  25. Van de Wetering, M. et al. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88, 789–799 (1997).

    CAS  PubMed  Google Scholar 

  26. Wehrli, M. et al. arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407, 527–530 (2000).

    CAS  PubMed  Google Scholar 

  27. Zusman, S. B. & Wieschaus, E. F. Requirements for zygotic gene activity during gastrulation in Drosophila melanogaster. Dev. Biol. 111, 359–371 (1985).

    CAS  PubMed  Google Scholar 

  28. Merrill, P. T., Sweeton, D. & Wieschaus, E. Requirements for autosomal gene activity during precellular stages of Drosophila melanogaster. Development 104, 495–509 (1988).

    CAS  PubMed  Google Scholar 

  29. Lee, L. A., Elfring, L. K., Bosco, G. & Orr-Weaver, T. L. A genetic screen for suppressors and enhancers of the Drosophila PAN GU cell cycle kinase identifies cyclin B as a target. Genetics 158, 1545–1556 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Simon, M. A. Signal transduction during the development of the Drosophila R7 photoreceptor. Dev. Biol. 166, 431–442 (1994).A review that describes several of the classic enhancer and suppressor screens that identified components of the Sevenless pathway.

    CAS  PubMed  Google Scholar 

  31. Simon, M. A., Dodson, G. S. & Rubin, G. M. An SH3–SH2–SH3 protein is required for p21Ras1 activation and binds to Sevenless and Sos proteins in vitro. Cell 73, 169–177 (1993).

    CAS  PubMed  Google Scholar 

  32. Simon, M. A. et al. Signal transduction pathway initiated by activation of the Sevenless tyrosine kinase receptor. Cold Spring Harb. Symp. Quant. Biol. 57, 375–380 (1992).

    CAS  PubMed  Google Scholar 

  33. Simon, M. A., Bowtell, D. D., Dodson, G. S., Laverty, T. R. & Rubin, G. M. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the Sevenless protein tyrosine kinase. Cell 67, 701–716 (1991).

    CAS  PubMed  Google Scholar 

  34. Allard, J. D., Chang, H. C., Herbst, R., McNeill, H. & Simon, M. A. The SH2-containing tyrosine phosphatase corkscrew is required during signaling by Sevenless, Ras1 and Raf. Development 122, 1137–1146 (1996).

    CAS  PubMed  Google Scholar 

  35. Rogge, R. D., Karlovich, C. A. & Banerjee, U. Genetic dissection of a neurodevelopmental pathway: Son of sevenless functions downstream of the sevenless and EGF receptor tyrosine kinases. Cell 64, 39–48 (1991).

    CAS  PubMed  Google Scholar 

  36. Olivier, J. P. et al. A Drosophila SH2–SH3 adaptor protein implicated in coupling the Sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. Cell 73, 179–191 (1993).

    CAS  PubMed  Google Scholar 

  37. Karim, F. D. et al. A screen for genes that function downstream of Ras1 during Drosophila eye development. Genetics 143, 315–329 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Dickson, B. J., Van der Straten, A., Dominguez, M. & Hafen, E. Mutations modulating Raf signaling in Drosophila eye development. Genetics 142, 163–171 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Therrien, M., Morrison, D. K., Wong, A. M. & Rubin, G. M. A genetic screen for modifiers of a kinase suppressor of Ras-dependent rough eye phenotype in Drosophila. Genetics 156, 1231–1242 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Therrien, M., Wong, A. M. & Rubin, G. M. CNK, a RAF-binding multidomain protein required for RAS signaling. Cell 95, 343–353 (1998).

    CAS  PubMed  Google Scholar 

  41. Chen, F. & Rebay, I. split ends, a new component of the Drosophila EGF receptor pathway, regulates development of midline glial cells. Curr. Biol. 10, 943–946 (2000).

    CAS  PubMed  Google Scholar 

  42. Rebay, I. et al. A genetic screen for novel components of the Ras/mitogen-activated protein kinase signaling pathway that interact with the yan gene of Drosophila identifies split ends, a new RNA recognition motif-containing protein. Genetics 154, 695–712 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Raftery, L. A., Twombly, V., Wharton, K. & Gelbart, W. M. Genetic screens to identify elements of the Decapentaplegic signaling pathway in Drosophila. Genetics 139, 241–254 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Casci, T., Vinos, J. & Freeman, M. Sprouty, an intracellular inhibitor of Ras signaling. Cell 96, 655–665 (1999).

    CAS  PubMed  Google Scholar 

  45. Kaminker, J. S., Singh, R., Lebestky, T., Yan, H. & Banerjee, U. Redundant function of Runt domain binding partners, Big brother and Brother, during Drosophila development. Development 128, 2639–2648 (2001).

    CAS  PubMed  Google Scholar 

  46. Barrett, K., Leptin, M. & Settleman, J. The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation. Cell 91, 905–915 (1997).

    CAS  PubMed  Google Scholar 

  47. Perrimon, N., Engstrom, L. & Mahowald, A. P. The effects of zygotic lethal mutations on female germ-line functions in Drosophila. Dev. Biol. 105, 404–414 (1984).

    CAS  PubMed  Google Scholar 

  48. Perrimon, N., Mohler, D., Engstrom, L. & Mahowald, A. X-linked female-sterile loci in Drosophila melanogaster. Genetics 113, 695–712 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 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 

  50. Xu, T., Wang, W., Zhang, S., Stewart, R. A. & Yu, W. Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121, 1053–1063 (1995).An excellent example of how clonal screens can identify types of mutation that cannot be found in traditional screens.

    CAS  PubMed  Google Scholar 

  51. Jiang, J. & Struhl, G. Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb. Nature 391, 493–496 (1998).

    CAS  PubMed  Google Scholar 

  52. Theodosiou, N. A., Zhang, S., Wang, W. Y. & Xu, T. slimb coordinates wg and dpp expression in the dorsal–ventral and anterior–posterior axes during limb development. Development 125, 3411–3416 (1998).

    CAS  PubMed  Google Scholar 

  53. Prout, M., Damania, Z., Soong, J., Fristrom, D. & Fristrom, J. W. Autosomal mutations affecting adhesion between wing surfaces in Drosophila melanogaster. Genetics 146, 275–285 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Walsh, E. P. & Brown, N. H. A screen to identify Drosophila genes required for integrin-mediated adhesion. Genetics 150, 791–805 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Gregory, S. L. & Brown, N. H. kakapo, a gene required for adhesion between and within cell layers in Drosophila, encodes a large cytoskeletal linker protein related to Plectin and Dystrophin. J. Cell Biol. 143, 1271–1282 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Chou, T.-B. & Perrimon, N. The autosomal FLP–DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics 144, 1673–1679 (1996).This powerful technique has made it possible to carry out germ-line clone screens to find the missing genes that are involved in embryonic pattern formation (described in references 57–62).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Chou, T.-B., Noll, E. & Perrimon, N. Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras. Development 119, 1359–1369 (1993).

    CAS  PubMed  Google Scholar 

  58. Perrimon, N., Lanjuin, A., Arnold, C. & Noll, E. Zygotic lethal mutations with maternal effect phenotypes in Drosophila melanogaster. II. Loci on the second and third chromosomes identified by P-element-induced mutations. Genetics 144, 1681–1692 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Bellaiche, Y., The, I. & Perrimon, N. Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature 394, 85–88 (1998).

    CAS  PubMed  Google Scholar 

  60. Häcker, U., Lin, X. & Perrimon, N. The Drosophila sugarless gene modulates Wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis. Development 124, 3565–3573 (1997).

    PubMed  Google Scholar 

  61. Lin, X., Buff, E. M., Perrimon, N. & Michelson, A. M. Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development. Development 126, 3715–3723 (1999).

    CAS  PubMed  Google Scholar 

  62. The, I., Bellaiche, Y. & Perrimon, N. Hedgehog movement is regulated throughtout velu-dependent synthesis of a heparan sulfate proteoglycan. Mol. Cell 4, 633–639 (1999).

    CAS  PubMed  Google Scholar 

  63. Luschnig, S., Krauss, J., Bohmann, K., Desjeux, I. & Nusslein-Volhard, C. The Drosophila SHC adaptor protein is required for signaling by a subset of receptor tyrosine kinases. Mol. Cell 5, 231–241 (2000).

    CAS  PubMed  Google Scholar 

  64. Duffy, J. B., Harrison, D. A. & Perrimon, N. Identifying loci required for follicular patterning using directed mosaics. Development 125, 2263–2271 (1998).

    CAS  PubMed  Google Scholar 

  65. Bai, J., Uehara, Y. & Montell, D. J. Regulation of invasive cell behavior by Taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer. Cell 103, 1047–1058 (2000).

    CAS  PubMed  Google Scholar 

  66. Liu, Y. & Montell, D. J. Identification of mutations that cause cell migration defects in mosaic clones. Development 126, 1869–1878 (1999).

    CAS  PubMed  Google Scholar 

  67. Liu, Y. & Montell, D. J. jing: a downstream target of slbo required for developmental control of border cell migration. Development 128, 321–330 (2001).

    CAS  PubMed  Google Scholar 

  68. Pai, L. M., Barcelo, G. & Schupbach, T. D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis. Cell 103, 51–61 (2000).

    CAS  PubMed  Google Scholar 

  69. Newsome, T. P., Asling, B. & Dickson, B. J. Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics. Development 127, 851–860 (2000).Describes an elegant technique for carrying out clonal screens in the eye using eye FLP and selection against non-mutant clones.

    CAS  PubMed  Google Scholar 

  70. Stowers, R. S. & Schwarz, T. L. A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype. Genetics 152, 1631–1639 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Morata, G. & Ripoll, P. Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev. Biol. 42, 211–221 (1975).

    CAS  PubMed  Google Scholar 

  72. Maurel-Zaffran, C., Suzuki, T., Gahmon, G., Treisman, J. E. & Dickson, B. J. Cell-autonomous and non-autonomous functions of Lar in R7 photoreceptor axon targeting. Neuron 32, 225–235 (2001).

    CAS  PubMed  Google Scholar 

  73. Clandinin, T. R. et al. Drosophila LAR regulates R1–R6 and R7 target specificity in the visual system. Neuron 32, 237–248 (2001).

    CAS  PubMed  Google Scholar 

  74. Lee, C. H., Herman, T., Clandinin, T. R., Lee, R. & Zipursky, S. L. N-cadherin regulates target specificity in the Drosophila visual system. Neuron 30, 437–450 (2001).

    CAS  PubMed  Google Scholar 

  75. Moberg, K. H., Bell, D. W., Wahrer, D. C., Haber, D. A. & Hariharan, I. K. Archipelago regulates cyclin E levels in Drosophila and is mutated in human cancer cell lines. Nature 413, 311–316 (2001).

    CAS  PubMed  Google Scholar 

  76. Tapon, N., Ito, N., Dickson, B. J., Treisman, J. E. & Hariharan, I. K. The Drosophila Tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105, 345–355 (2001).

    CAS  PubMed  Google Scholar 

  77. Potter, C. J., Huang, H. & Xu, T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105, 357–368 (2001).References 75–77 show how clonal screens can identify phenotypes that could not be found using other strategies.

    CAS  PubMed  Google Scholar 

  78. Pichaud, F. & Desplan, C. A new visualization approach for identifying mutations that affect differentiation and organization of the Drosophila ommatidia. Development 128, 815–826 (2001).

    CAS  PubMed  Google Scholar 

  79. Rørth, P. A modular misexpression screen in Drosophila detecting tissue-specific phenotypes. Proc. Natl Acad. Sci. USA 93, 12418–12422 (1996).References 79 and 80 describe how the Gal4/ UAS system has been adapted to carry out screens for genes that give a phenotype when misexpressed in a particular tissue.

    PubMed  PubMed Central  Google Scholar 

  80. Rørth, P. et al. Systematic gain-of-function genetics in Drosophila. Development 125, 1049–1057 (1998).

    PubMed  Google Scholar 

  81. Duchek, P., Somogyi, K., Jekely, G., Beccari, S. & Rørth, P. Guidance of cell migration by the Drosophila PDGF/VEGF receptor. Cell 107, 17–26 (2001).

    CAS  PubMed  Google Scholar 

  82. Duchek, P. & Rørth, P. Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis. Science 291, 131–133 (2001).

    CAS  PubMed  Google Scholar 

  83. Abdelilah-Seyfried, S. et al. A gain-of-function screen for genes that affect the development of the Drosophila adult external sensory organ. Genetics 155, 733–752 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Kraut, R., Menon, K. & Zinn, K. A gain-of-function screen for genes controlling motor axon guidance and synaptogenesis in Drosophila. Curr. Biol. 11, 417–430 (2001).

    CAS  PubMed  Google Scholar 

  85. Mata, J., Curado, S., Ephrussi, A. & Rorth, P. Tribbles coordinates mitosis and morphogenesis in Drosophila by regulating string/CDC25 proteolysis. Cell 101, 511–522 (2000).

    CAS  PubMed  Google Scholar 

  86. Carthew, R. W. Gene silencing by double-stranded RNA. Curr. Opin. Cell Biol. 13, 244–248 (2001).

    CAS  PubMed  Google Scholar 

  87. Fraser, A. G. et al. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408, 325–330 (2000).

    CAS  PubMed  Google Scholar 

  88. Gonczy, P. et al. Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III. Nature 408, 331–336 (2000).

    CAS  PubMed  Google Scholar 

  89. Spradling, A. C. et al. The Berkeley Drosophila Genome Project gene disruption project: single P-element insertions mutating 25% of vital Drosophila genes. Genetics 153, 135–177 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Sokolowski, M. B. Drosophila: genetics meets behaviour. Nature Rev. Genet. 2, 879–890 (2001).

    CAS  PubMed  Google Scholar 

  91. Micklem, D. R. et al. The mago nashi gene is required for the polarisation of the oocyte and the formation of perpendicular axes in Drosophila. Curr. Biol. 7, 468–478 (1997).

    CAS  PubMed  Google Scholar 

  92. Shulman, J. M., Benton, R. & St Johnston, D. The Drosophila homolog of C. elegans PAR-1 organizes the oocyte cytoskeleton and directs oskar mRNA localisation to the posterior pole. Cell 101, 1–20 (2000).

    Google Scholar 

  93. Greenspan, R. J. Fly Pushing: the Theory and Practice of Drosophila Genetics (Cold Spring Harbor Laboratory Press, New York, 1997).

  94. Berger, J. et al. Genetic mapping with SNP markers in Drosophila. Nature Genet. 29, 475–481 (2001).

    CAS  PubMed  Google Scholar 

  95. Martin, S. G., Dobi, K. C. & St Johnston, D. A rapid method to map mutations in Drosophila. Genome Biol. 2, 0036 (2001).

    Google Scholar 

  96. Fischer, J. A., Giniger, E., Maniatis, T. & Ptashne, M. GAL4 activates transcription in Drosophila. Nature 332, 853–856 (1988).

    CAS  PubMed  Google Scholar 

  97. 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 

  98. Golic, K. Site-specific recombination between homologous chromosomes in Drosophila. Science 252, 958–961 (1991).The first demonstration that the yeast Flp recombinase can be used to generate mitotic clones in Drosophila.

    CAS  PubMed  Google Scholar 

  99. Xu, T. & Rubin, G. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223–1237 (1993).The first Flp/ FRT clonal screen in Drosophila.

    CAS  PubMed  Google Scholar 

  100. Kidd, T., Russell, C., Goodman, C. S. & Tear, G. Dosage-sensitive and complementary functions of roundabout and commissureless control axon crossing of the CNS midline. Neuron 20, 25–33 (1998).

    CAS  PubMed  Google Scholar 

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Acknowledgements

I thank N. Brown, B. Dickson, M. Freeman, E. Hafen, B. Sanson and T. Xu for providing pictures, and S. Bray for her helpful comments on the manuscript. D.StJ. is supported by a Wellcome Trust Principal Fellowship.

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DATABASES

LocusLink 

ago

Argos

arm

arr

BMP4

Cbl

CHRD

comm

Csw

Dl

dp

Dpp

Drk

Dsh

Egfr

E(spl)

ey

Fz

Hh

hid

Lar

mago

Min

Notch

ovo

pan

par-1

Phyl

pio

Pten

rl

robo

Sev

sfl

sgl

SHH

slmb

sna

Sog

Sos

Spi

stau

sty

Su(dx)

Su(H)

Tor

Trbl

ttv

tuberous sclerosis complex 1 and 2

twi

VEGF

Wg

wts

zen 

Saccharomyces Genome Database 

Gal4

FURTHER INFORMATION

Berkeley Drosophila Genome Project

Bloomington Stock Center 

Genetic screening and testing 

FlyBase

Nature Reviews Genetics Focus on 'The art and design of genetics screens'

Szeged Stock Centre

Glossary

POLYTENE CHROMOSOME

A giant chromosome that is formed by many rounds of replication of the DNA. The replicated DNA molecules tightly align side-by-side in parallel register, which creates a non-mitotic chromosome that is visible by light microscopy.

PROTOSTOME–DEUTEROSTOME

The two principal divisions of animal phyla, based on how the mouth forms in the embryo.

BALANCER CHROMOSOME

A chromosome with one or more inverted segments that suppress recombination. They are used as genetic tools because they allow lethal mutations to be maintained without selection.

MATERNAL-EFFECT MUTATION

Homozygous-viable mutation that causes little or no phenotype in the mutant mothers, but leads to the development of abnormal offspring.

IPSILATERAL AXON

An axon that does not cross the midline.

SEGMENT-POLARITY GENE

A gene that is required for anteroposterior patterning within each segment, such as wingless, engrailed and hedgehog.

OMMATIDIA

The compound eye of Drosophila is formed from 800 ommatidia, each of which contains eight photoreceptor cells, surrounded by four cone cells that secrete the lens, and seven pigment cells.

IMAGINAL DISC

Sac-like infolding of the epithelium in the larva. They give rise to most of the external structures of the adult. Imaginal disc cells are set aside in the embryo and continue to divide until pupation, when they differentiate.

NOTUM

The dorsal or upper surface of the thoracic segment of any insect.

FOLLICLE STEM CELL

Each ovariole (chambers in the ovary through which the egg passes during development) contains 2–3 follicle stem cells, which produce the somatic follicle cells that surround the chambers. The follicle cells then differentiate into several cell types, including the border cells, which migrate from the anterior of the egg chamber towards the oocyte, where they contribute to the formation of the micropyle. At the end of oogenesis, the follicle cells secrete the eggshell and undergo apoptosis.

MINI-WHITE GENE

A truncated version of the white gene that is commonly used as the selectable marker in transformation constructs. One copy of the transgene usually produces yellow or orange eyes in a white mutant background, whereas two copies give more complete rescue and produce darker eye colours. This allows more than one transgene to be followed at a time, and flies that are either heterozygous or homozygous for a particular insertion to be distinguished.

ISOGENESIS

A way of homogenizing the genetic background of a line that is used for mutagenesis. In an isogenic stock, the two homologous chromosomes of each pair are identical, which ensures that no recessive lethal allele is present.

RNA INTERFERENCE

(RNAi). A process by which double-stranded RNA specifically silences the expression of homologous genes through degradation of their cognate mRNA.

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St Johnston, D. The art and design of genetic screens: Drosophila melanogaster. Nat Rev Genet 3, 176–188 (2002). https://doi.org/10.1038/nrg751

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