CoChat
Sign Up
Cited by 644Neurobiology and Insect Physiology ResearchDevelopmental Biology and Gene RegulationDiptera species taxonomy and behavior

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

The art and design of genetic screens: Drosophila melanogaster

St Johnston, Daniel·2002·Nature Reviews Genetics
DOI 10.1038/nrg751
Open this paper in CoChat — free account

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.

Overview

Integrity signals

Registry

Crossref · 10.1038/nrg751

Cites

0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Show all 0 references

Research works printed but not linked: 99

  1. Kohler, R. E. Lords of the Fly: Drosophila Genetics and the Experimental Life Vol. 15 (Univ. Chicago Press, Chicago, Illinois, 1994).
  2. Rubin, G. M. & Lewis, E. B. A brief history of Drosophila's contributions to genome research. Science 287, 2216–2218 (2000). · DOI
  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). · DOI
  4. Pearse, R. V. & Tabin, C.J. The molecular ZPA. J. Exp. Zool. 282, 677–690 (1998). · DOI
  5. Adams, M. D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000). · DOI
  6. Friedman, R. & Hughes, A. L. Pattern and timing of gene duplication in animal genomes. Genome Res. 11, 1842–1847 (2001). · DOI
  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). · DOI
  8. Feany, M. B. & Bender, W. W. A Drosophila model of Parkinson's disease. Nature 404, 394–398 (2000). · DOI
  9. Lewis, E. B. & Bacher, F. Methods of feeding ethyl methane sulphonate (EMS) to Drosophila males. Drosoph. Inf. Serv. 43, 193 (1968).
  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. · DOI
  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. · DOI
  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). · DOI
  14. Nüsslein-Volhard, C., Frohnhöfer, H. G. & Lehmann, R. Determination of anteroposterior polarity in Drosophila. Science 238, 1675–1681 (1987). · DOI
  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). · DOI
  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). · DOI
  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). · DOI
  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). · DOI
  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). · DOI
  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. · DOI
  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). · DOI
  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). · DOI
  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). · DOI
  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). · DOI · Paper page
  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). · DOI
  26. Wehrli, M. et al. arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407, 527–530 (2000). · DOI
  27. Zusman, S. B. & Wieschaus, E. F. Requirements for zygotic gene activity during gastrulation in Drosophila melanogaster. Dev. Biol. 111, 359–371 (1985). · DOI
  28. Merrill, P. T., Sweeton, D. & Wieschaus, E. Requirements for autosomal gene activity during precellular stages of Drosophila melanogaster. Development 104, 495–509 (1988). · DOI
  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). · DOI
  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. · DOI
  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). · DOI
  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). · DOI
  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). · DOI
  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). · DOI
  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). · DOI
  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). · DOI
  37. Karim, F. D. et al. A screen for genes that function downstream of Ras1 during Drosophila eye development. Genetics 143, 315–329 (1996). · DOI
  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). · DOI
  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). · DOI
  40. Therrien, M., Wong, A. M. & Rubin, G. M. CNK, a RAF-binding multidomain protein required for RAS signaling. Cell 95, 343–353 (1998). · DOI
  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). · DOI
  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). · DOI
  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). · DOI
  44. 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). · DOI
  45. 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). · DOI
  46. 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). · DOI
  47. Perrimon, N., Mohler, D., Engstrom, L. & Mahowald, A. X-linked female-sterile loci in Drosophila melanogaster. Genetics 113, 695–712 (1986). · DOI
  48. Golic, K. G. & Lindquist, S. The FLP recombinase of yeast catalyzes site-specific recombination in the Drosophila genome. Cell 59, 499–509 (1989). · DOI · Paper page
  49. 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. · DOI · Paper page
  50. 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). · DOI · Paper page
  51. 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). · DOI
  52. 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). · DOI
  53. Walsh, E. P. & Brown, N. H. A screen to identify Drosophila genes required for integrin-mediated adhesion. Genetics 150, 791–805 (1998). · DOI
  54. 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). · DOI
  55. 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). · DOI
  56. 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). · DOI
  57. 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). · DOI
  58. 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). · DOI
  59. 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). · DOI
  60. 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). · DOI
  61. 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). · DOI
  62. 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). · DOI
  63. Duffy, J. B., Harrison, D. A. & Perrimon, N. Identifying loci required for follicular patterning using directed mosaics. Development 125, 2263–2271 (1998). · DOI
  64. 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). · DOI
  65. Liu, Y. & Montell, D. J. Identification of mutations that cause cell migration defects in mosaic clones. Development 126, 1869–1878 (1999). · DOI
  66. Liu, Y. & Montell, D. J. jing: a downstream target of slbo required for developmental control of border cell migration. Development 128, 321–330 (2001). · DOI
  67. 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). · DOI
  68. 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. · DOI
  69. 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). · DOI
  70. Morata, G. & Ripoll, P. Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev. Biol. 42, 211–221 (1975). · DOI
  71. 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). · DOI
  72. Clandinin, T. R. et al. Drosophila LAR regulates R1–R6 and R7 target specificity in the visual system. Neuron 32, 237–248 (2001). · DOI
  73. 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). · DOI
  74. 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). · DOI
  75. 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). · DOI
  76. 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. · DOI
  77. 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). · DOI
  78. 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. · DOI
  79. Rørth, P. et al. Systematic gain-of-function genetics in Drosophila. Development 125, 1049–1057 (1998). · DOI
  80. 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). · DOI
  81. Duchek, P. & Rørth, P. Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis. Science 291, 131–133 (2001). · DOI
  82. 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). · DOI
  83. 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). · DOI
  84. 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). · DOI
  85. Carthew, R. W. Gene silencing by double-stranded RNA. Curr. Opin. Cell Biol. 13, 244–248 (2001). · DOI
  86. Fraser, A. G. et al. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408, 325–330 (2000). · DOI
  87. 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). · DOI
  88. 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). · DOI
  89. Sokolowski, M. B. Drosophila: genetics meets behaviour. Nature Rev. Genet. 2, 879–890 (2001). · DOI
  90. 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). · DOI · Paper page
  91. 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). · DOI
  92. Greenspan, R. J. Fly Pushing: the Theory and Practice of Drosophila Genetics (Cold Spring Harbor Laboratory Press, New York, 1997).
  93. Berger, J. et al. Genetic mapping with SNP markers in Drosophila. Nature Genet. 29, 475–481 (2001). · DOI
  94. Martin, S. G., Dobi, K. C. & St Johnston, D. A rapid method to map mutations in Drosophila. Genome Biol. 2, 0036 (2001). · DOI
  95. Fischer, J. A., Giniger, E., Maniatis, T. & Ptashne, M. GAL4 activates transcription in Drosophila. Nature 332, 853–856 (1988). · DOI
  96. Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993). · DOI
  97. 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. · DOI
  98. 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. · DOI
  99. 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). · DOI

Cited by

Sorted by citations

Items 301–400 of 547

Metadata

Authors
St Johnston, D.
Venue
Nature Reviews Genetics
Publisher
Springer Science and Business Media LLC
Published
2002-03
Volume
3
Issue
3
Pages
176-188
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
DOI
10.1038/nrg751
OpenAlex
W2027125425
Cited by
644
References
0
Citations by year
2026: 7 · 2025: 17 · 2024: 26 · 2023: 23 · 2022: 25 · 2021: 28 · 2020: 40 · 2019: 33 · 2018: 38 · 2017: 29 · 2016: 30 · 2015: 40 · 2014: 41 · 2013: 32 · 2012: 36
FWCI
1.76
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Diptera species taxonomy and behavior
Keywords
forward genetic screen, Drosophila melanogaster, modifier screen, embryonic patterning, signaling pathways
MeSH terms
Animals, Crosses, Genetic, Drosophila melanogaster, Enhancer Elements, Genetic, Eye, Female, Genetic Testing, Male, Phenotype, Gene Expression, Genes, Suppressor, Mutagenesis, Genes, Insect

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review