Natural variation in the regulation of neurodevelopmental genes modifies flight performance in Drosophila

Autoři: Adam N. Spierer aff001;  Jim A. Mossman aff001;  Samuel Pattillo Smith aff001;  Lorin Crawford aff002;  Sohini Ramachandran aff001;  David M. Rand aff001
Působiště autorů: Department of Ecology and Evolutionary Biology, Brown University, Providence, Rhode Island, United States of America aff001;  Center for Computational Molecular Biology, Brown University, Providence, Rhode Island, United States of America aff002;  Microsoft Research New England, Cambridge, Massachusetts, United States of America aff003
Vyšlo v časopise: Natural variation in the regulation of neurodevelopmental genes modifies flight performance in Drosophila. PLoS Genet 17(3): e1008887. doi:10.1371/journal.pgen.1008887
Kategorie: Research Article


The winged insects of the order Diptera are colloquially named for their most recognizable phenotype: flight. These insects rely on flight for a number of important life history traits, such as dispersal, foraging, and courtship. Despite the importance of flight, relatively little is known about the genetic architecture of flight performance. Accordingly, we sought to uncover the genetic modifiers of flight using a measure of flies’ reaction and response to an abrupt drop in a vertical flight column. We conducted a genome wide association study (GWAS) using 197 of the Drosophila Genetic Reference Panel (DGRP) lines, and identified a combination of additive and marginal variants, epistatic interactions, whole genes, and enrichment across interaction networks. Egfr, a highly pleiotropic developmental gene, was among the most significant additive variants identified. We functionally validated 13 of the additive candidate genes’ (Adgf-A/Adgf-A2/CG32181, bru1, CadN, flapper (CG11073), CG15236, flippy (CG9766), CREG, Dscam4, form3, fry, Lasp/CG9692, Pde6, Snoo), and introduce a novel approach to whole gene significance screens: PEGASUS_flies. Additionally, we identified ppk23, an Acid Sensing Ion Channel (ASIC) homolog, as an important hub for epistatic interactions. We propose a model that suggests genetic modifiers of wing and muscle morphology, nervous system development and function, BMP signaling, sexually dimorphic neural wiring, and gene regulation are all important for the observed differences flight performance in a natural population. Additionally, these results represent a snapshot of the genetic modifiers affecting drop-response flight performance in Drosophila, with implications for other insects.

Klíčová slova:

Animal flight – Drosophila melanogaster – Epistasis – Genetic engineering – Genetic networks – Genetic screens – Genetics – Insect flight


1. Brodsky AK. The evolution of insect flight: Oxford University Press; 1994.

2. Edwards JS. The evolution of insect flight: Implications for the evolution of the nervous system. Brain Behavior and Evolution. 1997;50(1):8–12. doi: 10.1159/000113317 WOS:A1997XE45100002. 9209762

3. Ugur B, Chen KC, Bellen HJ. Drosophila tools and assays for the study of human diseases. Disease Models & Mechanisms. 2016;9(3):235–44. doi: 10.1242/dmm.023762 WOS:000371439600003. 26935102

4. Pavlou HJ, Goodwin SF. Courtship behavior in Drosophila melanogaster: towards a ’courtship connectome’. Current Opinion in Neurobiology. 2013;23(1):76–83. doi: 10.1016/j.conb.2012.09.002 WOS:000314562900013. 23021897

5. Weitkunat M, Schnorrer F. A guide to study Drosophila muscle biology. Methods. 2014;68(1):2–14. doi: 10.1016/j.ymeth.2014.02.037 24625467

6. Liu XY, Li YI, Pritchard JK. Trans Effects on Gene Expression Can Drive Omnigenic Inheritance. Cell. 2019;177(4):1022–+. doi: 10.1016/j.cell.2019.04.014 WOS:000466843000020. 31051098

7. Boyle EA, Li YI, Pritchard JK. An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell. 2017;169(7):1177–86. doi: 10.1016/j.cell.2017.05.038 WOS:000403332400008. 28622505

8. Quijano JC, Stinchfield MJ, Zerlanko B, Gibbens YY, Takaesu NT, Hyman-Walsh C, et al. The Sno Oncogene Antagonizes Wingless Signaling during Wing Development in Drosophila. Plos One. 2010;5(7). doi: 10.1371/journal.pone.0011619 WOS:000279980800008. 20661280

9. Nongthomba U, Pasalodos-Sanchez S, Clark S, Clayton JD, Sparrow JC. Expression and function of the Drosophila ACT88F actin isoform is not restricted to the indirect flight muscles. Journal of muscle research and cell motility. 2001;22(2):111–9. doi: 10.1023/a:1010308326890 11519734

10. Montooth KL, Marden JH, Clark AG. Mapping determinants of variation in energy metabolism, respiration and flight in Drosophila. Genetics. 2003;165(2):623–35. 14573475

11. Kao SY, Nikonova E, Ravichandran K, Spletter ML. Dissection of Drosophila melanogaster Flight Muscles for Omics Approaches. Jove-Journal of Visualized Experiments. 2019;(152). doi: 10.3791/60309 WOS:000493379500080. 31680668

12. Okada H, Ebhardt HA, Vonesch SC, Aebersold R, Hafen E. Proteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster. Nature Communications. 2016;7. doi: 10.1038/ncomms12649 WOS:000384969200001. 27582081

13. Marcus JM. The development and evolution of crossveins in insect wings. Journal of Anatomy. 2001;199:211–6. doi: 10.1046/j.1469-7580.2001.19910211.x WOS:000170738500022. 11523825

14. Lobell AS, Kaspari RR, Negron YLS, Harbison ST. The Genetic Architecture of Ovariole Number in Drosophila melanogaster: Genes with Major, Quantitative, and Pleiotropic Effects. G3-Genes Genomes Genetics. 2017;7(7):2391–403. doi: 10.1534/g3.117.042390 WOS:000404991600035. 28550012

15. Watanabe K, Stringer S, Frei O, Mirkov MU, de Leeuw C, Polderman TJC, et al. A global overview of pleiotropy and genetic architecture in complex traits. Nature Genetics. 2019;51(9):1339–+. doi: 10.1038/s41588-019-0481-0 WOS:000484010800010. 31427789

16. Mackay TFC, Richards S, Stone EA, Barbadilla A, Ayroles JF, Zhu DH, et al. The Drosophila melanogaster Genetic Reference Panel. Nature. 2012;482(7384):173–8. doi: 10.1038/nature10811 WOS:000299994100029. 22318601

17. Huang W, Massouras A, Inoue Y, Peiffer J, Ramia M, Tarone AM, et al. Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines. Genome Research. 2014;24(7):1193–208. doi: 10.1101/gr.171546.113 WOS:000338185000013. 24714809

18. Arya GH, Magwire MM, Huang W, Serrano-Negron YL, Mackay TFC, Anholt RRH. The Genetic Basis for Variation in Olfactory Behavior in Drosophila melanogaster. Chemical Senses. 2015;40(4):233–43. doi: 10.1093/chemse/bjv001 WOS:000355703500004. 25687947

19. Chow CY, Wolfner MF, Clark AG. Large Neurological Component to Genetic Differences Underlying Biased Sperm Use in Drosophila. Genetics. 2013;193(1):177–85. doi: 10.1534/genetics.112.146357 WOS:000312894700011. 23105014

20. Battlay P, Leblanc PB, Green L, Garud NR, Schmidt JM, Fournier-Level A, et al. Structural Variants and Selective Sweep Foci Contribute to Insecticide Resistance in the Drosophila Genetic Reference Panel. G3-Genes Genomes Genetics. 2018;8(11):3489–97. doi: 10.1534/g3.118.200619 WOS:000449381500009. 30190421

21. Chow CY, Kelsey KJP, Wolfner MF, Clark AG. Candidate genetic modifiers of retinitis pigmentosa identified by exploiting natural variation in Drosophila. Human Molecular Genetics. 2016;25(4):651–9. doi: 10.1093/hmg/ddv502 WOS:000372151000003. 26662796

22. Carbone MA, Yamamoto A, Huang W, Lyman RA, Meadors TB, Yamamoto R, et al. Genetic architecture of natural variation in visual senescence in Drosophila. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(43):E6620–E9. doi: 10.1073/pnas.1613833113 WOS:000386087100012. 27791033

23. Zhou SS, Morozova TV, Hussain YN, Luoma SE, McCoy L, Yamamoto A, et al. The Genetic Basis for Variation in Sensitivity to Lead Toxicity in Drosophila melanogaster. Environmental Health Perspectives. 2016;124(7):1062–70. doi: 10.1289/ehp.1510513 WOS:000380749300029. 26859824

24. Montgomery SL, Vorojeikina D, Huang W, Mackay TFC, Anholt RRH, Rand MD. Genome-Wide Association Analysis of Tolerance to Methylmercury Toxicity in Drosophila Implicates Myogenic and Neuromuscular Developmental Pathways. Plos One. 2014;9(10). doi: 10.1371/journal.pone.0110375 WOS:000343943700033. 25360876

25. Nakka P, Raphael BJ, Ramachandran S. Gene and Network Analysis of Common Variants Reveals Novel Associations in Multiple Complex Diseases. Genetics. 2016;204(2):783–+. doi: 10.1534/genetics.116.188391 WOS:000385871400031. 27489002

26. Babcock DT, Ganetzky B. An Improved Method for Accurate and Rapid Measurement of Flight Performance in Drosophila. Jove-Journal of Visualized Experiments. 2014;(84). doi: 10.3791/51223 WOS:000348604100055. 24561810

27. Carbon S, Douglass E, Dunn N, Good B, Harris NL, Lewis SE, et al. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Research. 2019;47(D1):D330–D8. doi: 10.1093/nar/gky1055 WOS:000462587400049. 30395331

28. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nature Genetics. 2000;25(1):25–9. doi: 10.1038/75556 WOS:000086884000011. 10802651

29. Mackay TF, Huang W. Charting the genotype–phenotype map: lessons from the Drosophila melanogaster Genetic Reference Panel. Wiley Interdisciplinary Reviews: Developmental Biology. 2018;7(1). doi: 10.1002/wdev.289 28834395

30. Pitchers W, Nye J, Marquez EJ, Kowalski A, Dworkin I, Houle D. A Multivariate Genome-Wide Association Study of Wing Shape in Drosophila melanogaster. Genetics. 2019;211(4):1429–47. doi: 10.1534/genetics.118.301342 WOS:000463935700021. 30792267

31. Paul L, Wang SH, Manivannan SN, Bonanno L, Lewis S, Austin CL, et al. Dpp-induced Egfr signaling triggers postembryonic wing development in Drosophila. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(13):5058–63. doi: 10.1073/pnas.1217538110 WOS:000318031900048. 23479629

32. Crossman SH, Streichan SJ, Vincent JP. EGFR signaling coordinates patterning with cell survival during Drosophila epidermal development. Plos Biology. 2018;16(10). doi: 10.1371/journal.pbio.3000027 WOS:000449322300040. 30379844

33. Sibilia M, Kroismayr R, Lichtenberger BM, Natarajan A, Hecking M, Holcmann M. The epidermal growth factor receptor: from development to tumorigenesis. Differentiation. 2007;75(9):770–87. doi: 10.1111/j.1432-0436.2007.00238.x WOS:000250816400002. 17999740

34. Li XY, MacArthur S, Bourgon R, Nix D, Pollard DA, Iyer VN, et al. Transcription factors bind thousands of active and inactive regions in the Drosophila blastoderm. Plos Biology. 2008;6(2):365–88. doi: 10.1371/journal.pbio.0060027 WOS:000254928400023. 18271625

35. MacArthur S, Li XY, Li JY, Brown JB, Chu HC, Zeng L, et al. Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions. Genome Biology. 2009;10(7). doi: 10.1186/gb-2009-10-7-r80 WOS:000269309600015. 19627575

36. Moses AM, Pollard DA, Nix DA, Iyer VN, Li XY, Biggin MD, et al. Large-scale turnover of functional transcription factor binding sites in Drosophila. Plos Computational Biology. 2006;2(10):1219–31. doi: 10.1371/journal.pcbi.0020130 WOS:000241921500006. 17040121

37. Thomas S, Li XY, Sabo PJ, Sandstrom R, Thurman RE, Canfield TK, et al. Dynamic reprogramming of chromatin accessibility during Drosophila embryo development. Genome Biology. 2011;12(5). doi: 10.1186/gb-2011-12-5-r43 WOS:000295732700007. 21569360

38. dos Santos G, Schroeder AJ, Goodman JL, Strelets VB, Crosby MA, Thurmond J, et al. FlyBase: introduction of the Drosophila melanogaster Release 6 reference genome assembly and large-scale migration of genome annotations. Nucleic Acids Research. 2015;43(D1):D690–D7. doi: 10.1093/nar/gku1099 WOS:000350210400101. 25398896

39. Grumbling G, Strelets V, FlyBase C. FlyBase: anatomical data, images and queries. Nucleic Acids Research. 2006;34:D484–D8. doi: 10.1093/nar/gkj068 WOS:000239307700106. 16381917

40. Kofler R, Schlötterer C. Gowinda: unbiased analysis of gene set enrichment for genome-wide association studies. Bioinformatics. 2012;28(15):2084–5. doi: 10.1093/bioinformatics/bts315 22635606

41. Metaxakis A, Oehler S, Klinakis A, Savakis C. Minos as a genetic and genomic tool in Drosophila melanogaster. Genetics. 2005;171(2):571–81. doi: 10.1534/genetics.105.041848 WOS:000233194500014. 15972463

42. Bellen HJ, Levis RW, He YC, Carlson JW, Evans-Holm M, Bae E, et al. The Drosophila Gene Disruption Project: Progress Using Transposons With Distinctive Site Specificities. Genetics. 2011;188(3):731–U341. doi: 10.1534/genetics.111.126995 WOS:000292538900022. 21515576

43. Mummery-Widmer JL, Yamazaki M, Stoeger T, Novatchkova M, Bhalerao S, Chen D, et al. Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi. Nature. 2009;458(7241):987–U59. doi: 10.1038/nature07936 WOS:000265412900033. 19363474

44. Neumuller RA, Richter C, Fischer A, Novatchkova M, Neumuller KG, Knoblich JA. Genome-Wide Analysis of Self-Renewal in Drosophila Neural Stem Cells by Transgenic RNAi. Cell Stem Cell. 2011;8(5):580–93. doi: 10.1016/j.stem.2011.02.022 WOS:000290927600017. 21549331

45. Firth LC, Baker NE. Spitz from the retina regulates genes transcribed in the second mitotic wave, peripodial epithelium, glia and plasmatocytes of the Drosophila eye imaginal disc. Developmental Biology. 2007;307(2):521–38. doi: 10.1016/j.ydbio.2007.04.037 WOS:000248019100027. 17553483

46. Hummel T, Zipursky L. Afferent induction of olfactory glomeruli requires N-cadherin. Neuron. 2004;42(1):77–88. doi: 10.1016/s0896-6273(04)00158-8 WOS:000221458400009. 15066266

47. Hummel T, Vasconcelos ML, Clemens JC, Fishilevich Y, Vosshall LB, Zipursky SL. Axonal targeting of olfactory receptor neurons in Drosophila is controlled by Dscam. Neuron. 2003;37(2):221–31. doi: 10.1016/s0896-6273(02)01183-2 WOS:000181054900008. 12546818

48. Soba P, Zhu S, Emoto K, Younger S, Yang SJ, Yu HH, et al. Drosophila sensory neurons require Dscam for dendritic self-avoidance and proper dendritic field organization. Neuron. 2007;54(3):403–16. doi: 10.1016/j.neuron.2007.03.029 WOS:000246855700011. 17481394

49. Tadros W, Xu SW, Akin O, Yi CH, Shin GJE, Millard SS, et al. Dscam Proteins Direct Dendritic Targeting through Adhesion. Neuron. 2016;89(3):480–93. doi: 10.1016/j.neuron.2015.12.026 WOS:000373564900009. 26844831

50. Luo K. Signaling cross talk between TGF-β/Smad and other signaling pathways. Cold Spring Harbor perspectives in biology. 2017;9(1):a022137. doi: 10.1101/cshperspect.a022137 27836834

51. Krupp JJ, Yaich LE, Wessells RJ, Bodmer R. Identification of genetic loci that interact with cut during Drosophila wing-margin development. Genetics. 2005;170(4):1775–95. doi: 10.1534/genetics.105.043125 WOS:000232033300028. 15956666

52. Fernandes I, Schock F. The nebulin repeat protein Lasp regulates I-band architecture and filament spacing in myofibrils. Journal of Cell Biology. 2014;206(4):559–72. doi: 10.1083/jcb.201401094 WOS:000340739500009. 25113030

53. Spletter ML, Barz C, Yeroslaviz A, Schonbauer C, Ferreira IRS, Sarov M, et al. The RNA-binding protein Arrest (Bruno) regulates alternative splicing to enable myofibril maturation in Drosophila flight muscle. Embo Reports. 2015;16(2):178–91. doi: 10.15252/embr.201439791 WOS:000350695600009. 25532219

54. Kowalewski-Nimmerfall E, Schahs P, Maresch D, Rendic D, Kramer H, Mach L. Drosophila melanogaster cellular repressor of E1A-stimulated genes is a lysosomal protein essential for fly development. Biochimica Et Biophysica Acta-Molecular Cell Research. 2014;1843(12):2900–12. doi: 10.1016/j.bbamcr.2014.08.012 WOS:000343785700010. 25173815

55. Reyna MA, Leiserson MDM, Raphael BJ. Hierarchical HotNet: identifying hierarchies of altered subnetworks. Bioinformatics. 2018;34(17):972–80. doi: 10.1093/bioinformatics/bty613 WOS:000444317200045. 30423088

56. Huang W, Richards S, Carbone MA, Zhu DH, Anholt RRH, Ayroles JF, et al. Epistasis dominates the genetic architecture of Drosophila quantitative traits. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(39):15553–9. doi: 10.1073/pnas.1213423109 WOS:000309604500014. 22949659

57. Adams CM, Anderson MG, Motto DG, Price MP, Johnson WA, Welsh MJ. Ripped pocket and pickpocket, novel Drosophila DEG/ENaC subunits expressed in early development and in mechanosensory neurons. Journal of Cell Biology. 1998;140(1):143–52. doi: 10.1083/jcb.140.1.143 WOS:000071500600014. 9425162

58. Lu BK, LaMora A, Sun YS, Welsh MJ, Ben-Shahar Y. ppk23-Dependent Chemosensory Functions Contribute to Courtship Behavior in Drosophila melanogaster. Plos Genetics. 2012;8(3). doi: 10.1371/journal.pgen.1002587 WOS:000302254800062. 22438833

59. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9(1):559. doi: 10.1186/1471-2105-9-559 19114008

60. Huang W, Carbone MA, Magwire MM, Peiffer JA, Lyman RF, Stone EA, et al. Genetic basis of transcriptome diversity in Drosophila melanogaster. Proceedings of the National Academy of Sciences. 2015;112(44):E6010–E9. doi: 10.1073/pnas.1519159112 26483487

61. Crawford L, Zeng P, Mukherjee S, Zhou X. Detecting epistasis with the marginal epistasis test in genetic mapping studies of quantitative traits. Plos Genetics. 2017;13(7). doi: 10.1371/journal.pgen.1006869 WOS:000406615300011. 28746338

62. Fuerst PG, Burgess RW. Adhesion molecules in establishing retinal circuitry. Current Opinion in Neurobiology. 2009;19(4):389–94. doi: 10.1016/j.conb.2009.07.013 WOS:000270107600007. 19660931

63. Emoto K, He Y, Ye B, Grueber WB, Adler PN, Jan LY, et al. Control of dendritic branching and tiling by the tricornered-kinase/furry signaling pathway in Drosophila sensory neurons. Cell. 2004;119(2):245–56. doi: 10.1016/j.cell.2004.09.036 WOS:000224577200012. 15479641

64. Matsubara D, Horiuchi SY, Shimono K, Usui T, Uemura T. The seven-pass transmembrane cadherin Flamingo controls dendritic self-avoidance via its binding to a LIM domain protein, Espinas, in Drosophila sensory neurons. Genes & Development. 2011;25(18):1982–96. doi: 10.1101/gad.16531611 WOS:000295082400009. 21937715

65. Zhan XL, Clemens JC, Neves G, Hattori D, Flanagan JJ, Hummel T, et al. Analysis of Dscam diversity in regulating axon guidance in Drosophila mushroom bodies. Neuron. 2004;43(5):673–86. doi: 10.1016/j.neuron.2004.07.020 WOS:000223691900013. 15339649

66. Neves G, Zucker J, Daly M, Chess A. Stochastic yet biased expression of multiple Dscam splice variants by individual cells. Nature Genetics. 2004;36(3):240–6. doi: 10.1038/ng1299 WOS:000189250400012. 14758360

67. Thistle R, Cameron P, Ghorayshi A, Dennison L, Scott K. Contact chemoreceptors mediate male-male repulsion and male-female attraction during Drosophila courtship. Cell. 2012;149(5):1140–51. doi: 10.1016/j.cell.2012.03.045 22632976

68. Guo Y, Wang Y, Wang Q, Wang Z. The role of PPK26 in Drosophila larval mechanical nociception. Cell reports. 2014;9(4):1183–90. doi: 10.1016/j.celrep.2014.10.020 25457610

69. Gorczyca DA, Younger S, Meltzer S, Kim SE, Cheng L, Song W, et al. Identification of Ppk26, a DEG/ENaC channel functioning with Ppk1 in a mutually dependent manner to guide locomotion behavior in Drosophila. Cell reports. 2014;9(4):1446–58. doi: 10.1016/j.celrep.2014.10.034 25456135

70. Elkins T, Ganetzky B, Wu CF. A DROSOPHILA MUTATION THAT ELIMINATES A CALCIUM-DEPENDENT POTASSIUM CURRENT. Proceedings of the National Academy of Sciences of the United States of America. 1986;83(21):8415–9. doi: 10.1073/pnas.83.21.8415 WOS:A1986E643100082. 2430288



73. Iyengar A, Wu CF. Flight and Seizure Motor Patterns in Drosophila Mutants: Simultaneous Acoustic and Electrophysiological Recordings of Wing Beats and Flight Muscle Activity. Journal of Neurogenetics. 2014;28(3–4):316–28. doi: 10.3109/01677063.2014.957827 WOS:000344555700015. 25159538

74. Wilson DM. The central nervous control of flight in a locust. Journal of Experimental Biology. 1961;38(2):471–90.

75. Ainsley JA, Kim MJ, Wegman LJ, Pettus JM, Johnson WA. Sensory mechanisms controlling the timing of larval developmental and behavioral transitions require the Drosophila DEG/ENaC subunit, Pickpocket1. Developmental Biology. 2008;322(1):46–55. doi: 10.1016/j.ydbio.2008.07.003 WOS:000259790000005. 18674528

76. Ainsley JA, Pettus JM, Bosenko D, Gerstein CE, Zinkevich N, Anderson MG, et al. Enhanced locomotion caused by loss of the Drosophila DEG/ENaC protein pickpocket1. Current Biology. 2003;13(17):1557–63. doi: 10.1016/s0960-9822(03)00596-7 WOS:000185171300028. 12956960

77. Orr BO, Gorczyca D, Younger MA, Jan LY, Jan YN, Davis GW. Composition and Control of a Deg/ENaC Channel during Presynaptic Homeostatic Plasticity. Cell Reports. 2017;20(8):1855–66. doi: 10.1016/j.celrep.2017.07.074 WOS:000408154300011. 28834749

78. Younger MA, Muller M, Tong A, Pym EC, Davis GW. A Presynaptic ENaC Channel Drives Homeostatic Plasticity. Neuron. 2013;79(6):1183–96. doi: 10.1016/j.neuron.2013.06.048 WOS:000330329600015. 23973209

79. Kimura KI, Ote M, Tazawa T, Yamamoto D. Fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain. Nature. 2005;438(7065):229–33. doi: 10.1038/nature04229 WOS:000233133500050. 16281036

80. Northcutt AJ, Schulz DJ. Molecular mechanisms of homeostatic plasticity in central pattern generator networks. Developmental Neurobiology. 2020;80(1–2):58–69. doi: 10.1002/dneu.22727 WOS:000502572300001. 31778295

81. Ben-Shahar Y. Sensory Functions for Degenerin/Epithelial Sodium Channels (DEG/ENaC). In: Friedmann T, Dunlap JC, Goodwin SF, editors. Advances in Genetics, Vol 76. Advances in Genetics. 762011. p. 1–26. doi: 10.1016/B978-0-12-386481-9.00001-8 22099690

82. Gendron CM, Kuo TH, Harvanek ZM, Chung BY, Yew JY, Dierick HA, et al. Drosophila Life Span and Physiology Are Modulated by Sexual Perception and Reward. Science. 2014;343(6170):544–8. doi: 10.1126/science.1243339 WOS:000330343700048. 24292624

83. Yu JY, Kanai MI, Demir E, Jefferis G, Dickson BJ. Cellular Organization of the Neural Circuit that Drives Drosophila Courtship Behavior. Current Biology. 2010;20(18):1602–14. doi: 10.1016/j.cub.2010.08.025 WOS:000282385600020. 20832315

84. Shirangi TR, Wong AM, Truman JW, Stern DL. Doublesex Regulates the Connectivity of a Neural Circuit Controlling Drosophila Male Courtship Song. Developmental Cell. 2016;37(6):533–44. doi: 10.1016/j.devcel.2016.05.012 WOS:000378204200008. 27326931

85. Rezaval C, Pavlou HJ, Dornan AJ, Chan YB, Kravitz EA, Goodwin SF. Neural Circuitry Underlying Drosophila Female Postmating Behavioral Responses. Current Biology. 2012;22(13):1155–65. doi: 10.1016/j.cub.2012.04.062 WOS:000306379600018. 22658598

86. Mardahl-Dumesnil M, Fowler VM. Thin filaments elongate from their pointed ends during myofibril assembly in Drosophila indirect flight muscle. Journal of Cell Biology. 2001;155(6):1043–53. doi: 10.1083/jcb.200108026 WOS:000172730200017. 11739412

87. Hevia CF, Lopez-Varea A, Esteban N, de Celis JF. A Search for Genes Mediating the Growth-Promoting Function of TGF beta in the Drosophila melanogaster Wing Disc. Genetics. 2017;206(1):231–49. doi: 10.1534/genetics.116.197228 WOS:000401127800016. 28315837

88. Cruz C, Glavic A, Casado M, de Celis JF. A Gain-of-Function Screen Identifying Genes Required for Growth and Pattern Formation of the Drosophila melanogaster Wing. Genetics. 2009;183(3):1005–26. doi: 10.1534/genetics.109.107748 WOS:000272295800021. 19737745

89. Yu K, Sturtevant MA, Biehs B, Francois V, Padgett RW, Blackman RK, et al. The Drosophila decapentaplegic and short gastrulation genes function antagonistically during adult wing vein development. Development. 1996;122(12):4033–44. WOS:A1996WC55400034. 9012523

90. Bangi E, Wharton K. Dual function of the Drosophila Alk1/Alk2 ortholog Saxophone shapes the Bmp activity gradient in the wing imaginal disc. Development. 2006;133(17):3295–303. doi: 10.1242/dev.02513 16887821

91. Bangi E, Wharton K. Dpp and Gbb exhibit different effective ranges in the establishment of the BMP activity gradient critical for Drosophila wing patterning. Developmental biology. 2006;295(1):178–93. doi: 10.1016/j.ydbio.2006.03.021 16643887

92. Ball RW, Warren-Paquin M, Tsurudome K, Liao EH, Elazzouzi F, Cavanagh C, et al. Retrograde BMP Signaling Controls Synaptic Growth at the NMJ by Regulating Trio Expression in Motor Neurons. Neuron. 2010;66(4):536–49. doi: 10.1016/j.neuron.2010.04.011 WOS:000278771100009. 20510858

93. Fischer S, Bayersdorfer F, Harant E, Reng R, Arndt S, Bosserhoff AK, et al. fussel (fuss)—A Negative Regulator of BMP Signaling in Drosophila melanogaster. Plos One. 2012;7(8). doi: 10.1371/journal.pone.0042349 WOS:000307437900031. 22879948

94. Takaesu NT, Hyman-Walsh C, Ye Y, Wisotzkey RG, Stinchfield MJ, O’Connor MB, et al. dSno facilitates Baboon signaling in the Drosophila brain by switching the affinity of Medea away from Mad and toward dSmad2. Genetics. 2006;174(3):1299–313. doi: 10.1534/genetics.106.064956 16951053

95. O’Connor MB, Umulis D, Othmer HG, Blair SS. Shaping BMP morphogen gradients in the Drosophila embryo and pupal wing. Development. 2006;133(2):183–93. WOS:000235345700001. doi: 10.1242/dev.02214 16368928

96. Wharton KA, Serpe M. Fine-tuned shuttles for bone morphogenetic proteins. Current Opinion in Genetics & Development. 2013;23(4):374–84. doi: 10.1016/j.gde.2013.04.012 WOS:000324362900003. 23735641

97. Wittkopp PJ, Haerum BK, Clark AG. Evolutionary changes in cis and trans gene regulation. Nature. 2004;430(6995):85–8. doi: 10.1038/nature02698 WOS:000222356800048. 15229602

98. Hacker U, Grossniklaus U, Gehring WJ, Jackle H. DEVELOPMENTALLY REGULATED DROSOPHILA GENE FAMILY ENCODING THE FORK HEAD DOMAIN. Proceedings of the National Academy of Sciences of the United States of America. 1992;89(18):8754–8. doi: 10.1073/pnas.89.18.8754 WOS:A1992JN50300071. 1356269

99. Dickinson MH, Lehmann F-O, Sane SP. Wing rotation and the aerodynamic basis of insect flight. Science. 1999;284(5422):1954–60. doi: 10.1126/science.284.5422.1954 10373107

100. Bellen HJ, Levis RW, He Y, Carlson JW, Evans-Holm M, Bae E, et al. The drosophila gene disruption project: progress using transposons with distinctive site-specificities. Genetics. 2011:genetics. 111.126995. doi: 10.1534/genetics.111.126995 21515576

101. Elgin S, Miller D. Special techniques for tissue isolation and injection. II. Mass rearing of flies and mass production and harvesting of embryos. Genetics and biology of Drosophila. 1978.

102. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nature Methods. 2012;9(7):676–82. doi: 10.1038/nmeth.2019 WOS:000305942200021. 22743772

103. Das J, Yu HY. HINT: High-quality protein interactomes and their applications in understanding human disease. Bmc Systems Biology. 2012;6. doi: 10.1186/1752-0509-6-92 WOS:000310442400001. 22846459

104. Yu JK, Pacifico S, Liu GZ, Finley RL. DroID: the Drosophila Interactions Database, a comprehensive resource for annotated gene and protein interactions. Bmc Genomics. 2008;9. doi: 10.1186/1471-2164-9-9 WOS:000260678600001. 18186939

105. Murali T, Pacifico S, Yu JK, Guest S, Roberts GG, Finley RL. DroID 2011: a comprehensive, integrated resource for protein, transcription factor, RNA and gene interactions for Drosophila. Nucleic Acids Research. 2011;39:D736–D43. doi: 10.1093/nar/gkq1092 WOS:000285831700117. 21036869

106. Hu YH, Flockhart I, Vinayagam A, Bergwitz C, Berger B, Perrimon N, et al. An integrative approach to ortholog prediction for disease-focused and other functional studies. Bmc Bioinformatics. 2011;12(1):357. doi: 10.1186/1471-2105-12-357 WOS:000295225400001. 21880147

107. Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. Bmc Bioinformatics. 2009;10. doi: 10.1186/1471-2105-10-10 WOS:000264007400001. 19133123

108. Eden E, Lipson D, Yogev S, Yakhini Z. Discovering motifs in ranked lists of DNA sequences. Plos Computational Biology. 2007;3(3):508–22. doi: 10.1371/journal.pcbi.0030039 WOS:000246191000017. 17381235

109. Browning SR, Browning BL. Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. American Journal of Human Genetics. 2007;81(5):1084–97. doi: 10.1086/521987 WOS:000250480900018. 17924348

110. Browning BL, Browning SR. Genotype Imputation with Millions of Reference Samples. American Journal of Human Genetics. 2016;98(1):116–26. doi: 10.1016/j.ajhg.2015.11.020 WOS:000368050800009. 26748515

111. Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, et al. The variant call format and VCFtools. Bioinformatics. 2011;27(15):2156–8. doi: 10.1093/bioinformatics/btr330 WOS:000292778700023. 21653522

112. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics. 2007;81(3):559–75. doi: 10.1086/519795 WOS:000249128200012. 17701901

113. Frise E, Hammonds AS, Celniker SE. Systematic image-driven analysis of the spatial Drosophila embryonic expression landscape. Molecular Systems Biology. 2010;6. doi: 10.1038/msb.2009.102 WOS:000274193500002. 20087342

114. Chintapalli VR, Wang J, Dow JAT. Using FlyAtlas to identify better Drosophila melanogaster models of human disease. Nature Genetics. 2007;39(6):715–20. doi: 10.1038/ng2049 WOS:000246859100012. 17534367

115. Consortium TAoGR. Alliance of Genome Resources Portal: unified model organism research platform. Nucleic acids research. 2020;48(D1):D650–D8. doi: 10.1093/nar/gkz813 31552413

116. Gaudet P, Livstone MS, Lewis SE, Thomas PD. Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in Bioinformatics. 2011;12(5):449–62. doi: 10.1093/bib/bbr042 WOS:000295171700010. 21873635

117. Karr TL. Fruit flies and the sperm proteome. Human Molecular Genetics. 2007;16:R124–R33. doi: 10.1093/hmg/ddm252 WOS:000251165500002. 17911156

118. Casas-Vila N, Bluhm A, Sayols S, Dinges N, Dejung M, Altenhein T, et al. The developmental proteome of Drosophila melanogaster. Genome Research. 2017;27(7):1273–85. doi: 10.1101/gr.213694.116 WOS:000404735500016. 28381612

119. Brown JB, Boley N, Eisman R, May GE, Stoiber MH, Duff MO, et al. Diversity and dynamics of the Drosophila transcriptome. Nature. 2014;512(7515):393–9. doi: 10.1038/nature12962 WOS:000340840600025. 24670639

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