The Sex Determination Gene transformer Regulates Male-Female Differences in Drosophila Body Size

PLoS Genetics

Volumn 11, Issue 12, 2015, Pages

  Rideout, Elizabeth J ^a,b   Narsaiya, Marcus S ^b   Grewal, Savraj S ^a  

^a UNIVERSITY OF CALGARY   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DNA BINDING PROTEIN; DROSOPHILA PROTEIN; DSX PROTEIN, DROSOPHILA; FRU PROTEIN, DROSOPHILA; INSULIN; NERVE PROTEIN; NUCLEAR PROTEIN; TRANSCRIPTION FACTOR; TRANSFORMER PROTEIN, DROSOPHILA;

ANIMAL; BODY SIZE; BRAIN; DROSOPHILA; FAT PAD; FEMALE; GENETICS; GROWTH, DEVELOPMENT AND AGING; MALE; METABOLISM; SEX DETERMINATION PROCESS; SEXUAL DEVELOPMENT;

ANIMALS; BODY SIZE; BRAIN; DNA-BINDING PROTEINS; DROSOPHILA; DROSOPHILA PROTEINS; FAT BODY; FEMALE; INSULIN; MALE; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; SEX CHARACTERISTICS; SEX DETERMINATION PROCESSES; TRANSCRIPTION FACTORS;

EID: 84953280392     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1005683     Document Type: Article

References (103)

1. Edgar BA, (2006) How flies get their size: genetics meets physiology. Nature reviews. Genetics 7(12):907–916. 17139322
2. Edgar BA, (1999) From small flies come big discoveries about size control. Nature cell biology 1(8):E191–193. 10587651
3. Stillwell RC, Blanckenhorn WU, Teder T, Davidowitz G, Fox CW, (2010) Sex Differences in Phenotypic Plasticity Affect Variation in Sexual Size Dimorphism in Insects: From Physiology to Evolution. Annu Rev Entomol 55:227–245. doi: 10.1146/annurev-ento-112408-085500 19728836
4. Fairbairn DJ, (1997) Allometry for sexual size dimorphism: Pattern and process in the coevolution of body size in males and females. Annu Rev Ecol Syst 28:659–687.
5. Testa ND, Ghosh SM, Shingleton AW, (2013) Sex-specific weight loss mediates sexual size dimorphism in Drosophila melanogaster. PloS one 8(3):e58936. doi: 10.1371/journal.pone.0058936 23555608
6. Nijhout HF, et al. (2014) The developmental control of size in insects. Wiley interdisciplinary reviews. Developmental biology 3(1):113–134. doi: 10.1002/wdev.124 24902837
7. Hietakangas V, Cohen SM, (2009) Regulation of tissue growth through nutrient sensing. Annual review of genetics 43:389–410. doi: 10.1146/annurev-genet-102108-134815 19694515
8. Hall MN, Raff M., Thomas G., (2004) Cell growth: control of cell size. (Cold Spring Harbor Laboratory Press, New York).
9. Conlon I, Raff M, (1999) Size control in animal development. Cell 96(2):235–244. 9988218
10. Bridges CB, (1921) Triploid intersexes in Drosophila melanogaster. Science 54(1394) 252–254. 17769897
11. Salz HK, Erickson JW, (2010) Sex determination in Drosophila: The view from the top. Fly 4(1):60–70. 20160499
12. Cline TW, (1978) Two closely linked mutations in Drosophila melanogaster that are lethal to opposite sexes and interact with daughterless. Genetics 90(4):683–698. 105964
13. Inoue K, Hoshijima K, Sakamoto H, Shimura Y, (1990) Binding of the Drosophila sex-lethal gene product to the alternative splice site of transformer primary transcript. Nature 344(6265):461–463. 1690860
14. Belote JM, McKeown M, Boggs RT, Ohkawa R, Sosnowski BA, (1989) Molecular genetics of transformer, a genetic switch controlling sexual differentiation in Drosophila. Developmental genetics 10(3):143–154. 2472240
15. Boggs RT, Gregor P, Idriss S, Belote JM, McKeown M, (1987) Regulation of sexual differentiation in D. melanogaster via alternative splicing of RNA from the transformer gene. Cell 50(5):739–747. 2441872
16. Sosnowski BA, Belote JM, McKeown M, (1989) Sex-specific alternative splicing of RNA from the transformer gene results from sequence-dependent splice site blockage. Cell 58(3):449–459. 2503251
17. Heinrichs V, Ryner LC, Baker BS, (1998) Regulation of sex-specific selection of fruitless 5' splice sites by transformer and transformer-2. Molecular and cellular biology 18(1):450–458. 9418892
18. Ryner LC, et al. (1996) Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene. Cell 87(6):1079–1089. 8978612
19. Hoshijima K, Inoue K, Higuchi I, Sakamoto H, Shimura Y, (1991) Control of doublesex alternative splicing by transformer and transformer-2 in Drosophila. Science 252(5007):833–836. 1902987
20. Inoue K, Hoshijima K, Higuchi I, Sakamoto H, Shimura Y, (1992) Binding of the Drosophila transformer and transformer-2 proteins to the regulatory elements of doublesex primary transcript for sex-specific RNA processing. Proceedings of the National Academy of Sciences of the United States of America 89(17):8092–8096. 1518835
21. Burtis KC, Baker BS, (1989) Drosophila doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell 56(6):997–1010. 2493994
22. Nagoshi RN, McKeown M, Burtis KC, Belote JM, Baker BS, (1988) The control of alternative splicing at genes regulating sexual differentiation in D. melanogaster. Cell 53(2):229–236. 3129196
23. Cline TW, (1984) Autoregulatory functioning of a Drosophila gene product that establish es and maintains the sexually determined state. Genetics 107(2):231–277. 6735170
24. Cline TW, Meyer BJ, (1996) Vive la difference: males vs females in flies vs worms. Annual review of genetics 30:637–702. 8982468
25. Brown EH, King RC, (1961) Studies on the Expression of the Transformer Gene of Drosophila Melanogaster. Genetics 46(2):143–156. 17248040
26. Siera SG, Cline TW, (2008) Sexual back talk with evolutionary implications: stimulation of the Drosophila sex-determination gene sex-lethal by its target transformer. Genetics 180 (4): 1963–1981. doi: 10.1534/genetics.108.093898 18845845
27. Alpatov WW, (1930) Phenotypical variation in body and cell size of Drosophila melanogaster. Biol Bull-Us 58(1):85–103.
28. Garcia-Bellido A, Ripoll P, (1978) Cell lineage and differentiation in Drosophila. Results and problems in cell differentiation 9:119–156. 373037
29. Horabin JI, (2005) Splitting the Hedgehog signal: sex and patterning in Drosophila. Development 132(21):4801–4810. 16207758
30. Baker BS, Belote JM, (1983) Sex determination and dosage compensation in Drosophila melanogaster. Annual review of genetics 17:345–393. 6421227
31. Rodenfels J, et al. (2014) Production of systemically circulating Hedgehog by the intestine couples nutrition to growth and development. Genes & development 28(23):2636–2651.
32. Rajan A, Perrimon N, (2012) Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Cell 151(1):123–137. doi: 10.1016/j.cell.2012.08.019 23021220
33. Geminard C, Rulifson EJ, Leopold P, (2009) Remote control of insulin secretion by fat cells in Drosophila. Cell metabolism 10(3):199–207. doi: 10.1016/j.cmet.2009.08.002 19723496
34. Colombani J, et al. (2003) A nutrient sensor mechanism controls Drosophila growth. Cell 114(6):739–749. 14505573
35. Patel MN, Knight CG, Karageorgi C, Leroi AM, (2002) Evolution of germ-line signals that regulate growth and aging in nematodes. Proceedings of the National Academy of Sciences of the United States of America 99(2):769–774. 11805331
36. Rideout EJ, Billeter JC, Goodwin SF, (2007) The sex-determination genes fruitless and doublesex specify a neural substrate required for courtship song. Current biology: CB 17(17):1473–1478. 17716899
37. Rideout EJ, Dornan AJ, Neville MC, Eadie S, Goodwin SF, (2010) Control of sexual differentiation and behavior by the doublesex gene in Drosophila melanogaster. Nature neuroscience 13(4):458–466. doi: 10.1038/nn.2515 20305646
38. Sanders LE, Arbeitman MN, (2008) Doublesex establishes sexual dimorphism in the Drosophila central nervous system in an isoform-dependent manner by directing cell number. Developmental biology 320(2):378–390. doi: 10.1016/j.ydbio.2008.05.543 18599032
39. Robinett CC, Vaughan AG, Knapp JM, Baker BS, (2010) Sex and the single cell. II. There is a time and place for sex. PLoS biology 8(5):e1000365. doi: 10.1371/journal.pbio.1000365 20454565
40. Lee G, Hall JC, Park JH, (2002) Doublesex gene expression in the central nervous system of Drosophila melanogaster. Journal of neurogenetics 16(4):229–248. 12745633
41. Lee G, et al. (2000) Spatial, temporal, and sexually dimorphic expression patterns of the fruitless gene in the Drosophila central nervous system. Journal of neurobiology 43(4):404–426. 10861565
42. Camara N, Whitworth C, Van Doren M, (2008) The creation of sexual dimorphism in the Drosophila soma. Current topics in developmental biology 83:65–107. doi: 10.1016/S0070-2153(08)00403-1 19118664
43. Billeter JC, Rideout EJ, Dornan AJ, Goodwin SF, (2006) Control of male sexual behavior in Drosophila by the sex determination pathway. Current biology: CB 16(17):R766–776. 16950103
44. Demir E, Dickson BJ, (2005) fruitless splicing specifies male courtship behavior in Drosophila. Cell 121(5):785–794. 15935764
45. Grewal SS, (2009) Insulin/TOR signaling in growth and homeostasis: a view from the fly world. The international journal of biochemistry & cell biology 41(5):1006–1010.
46. Oldham S, Hafen E, (2003) Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends in cell biology 13(2):79–85. 12559758
47. Britton JS, Lockwood WK, Li L, Cohen SM, Edgar BA, (2002) Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Developmental cell 2(2):239–249. 11832249
48. Oldham S, Montagne J, Radimerski T, Thomas G, Hafen E, (2000) Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes & development 14(21):2689–2694.
49. Zhang H, Stallock JP, Ng JC, Reinhard C, Neufeld TP, (2000) Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes & development 14(21):2712–2724.
50. Radimerski T, et al. (2002) dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1. Nature cell biology 4(3):251–255. 11862217
51. Puig O, Marr MT, Ruhf ML, Tijan R, (2003) Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Genes Dev. 17(16): 2006–2020. 12893776
52. Alic N, et al. (2011) Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. Molecular systems biology 7:502. doi: 10.1038/msb.2011.36 21694719
53. Teleman AA, Hietakangas V, Sayadian AC, Cohen SM, (2008) Nutritional control of protein biosynthetic capacity by insulin via Myc in Drosophila. Cell metabolism 7(1):21–32. doi: 10.1016/j.cmet.2007.11.010 18177722
54. Junger MA, et al. (2003) The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. Journal of biology 2(3):20. 12908874
55. Zhang W, et al. (2013) ER stress potentiates insulin resistance through PERK-mediated FOXO phosphorylation. Genes Dev. 27(4): 441–449. doi: 10.1101/gad.201731.112 23431056
56. Teleman AA, Chen YW, Cohen SM, (2005) Drosophila Melted modulates FOXO and TOR activity. Dev. Cell 9(2): 271–281. 16054033
57. Ikeya T, Galic M, Belawat P, Nairz K, Hafen E, (2002) Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila. Current biology 12(15):1293–1300. 12176357
58. Brogiolo W, et al. (2001) An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Current biology 11(4):213–221. 11250149
59. Badyaev AV, (2002) Growing apart: an ontogenetic perspective on the evolution of sexual size dimorphism. Trends Ecol Evol 17(8):369–378.
60. Graham P, Penn JK, Schedl P, (2003) Masters change, slaves remain. BioEssays: news and reviews in molecular, cellular and developmental biology 25(1):1–4.
61. Geuverink E, Beukeboom LW, (2014) Phylogenetic distribution and evolutionary dynamics of the sex determination genes doublesex and transformer in insects. Sexual development: genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 8(1–3):38–49.
62. Gempe T, Beye M, (2011) Function and evolution of sex determination mechanisms, genes and pathways in insects. Bioessays 33(1):52–60. doi: 10.1002/bies.201000043 21110346
63. Evans DS, Cline TW, (2013) Drosophila switch gene Sex-lethal can bypass its switch-gene target transformer to regulate aspects of female behaviour. Proceedings of the National Academy of Sciences of the United States of America 110(47): E4474–4481. doi: 10.1073/pnas.1319063110 24191002
64. Honek A, (1993) Intraspecific Variation in Body Size and Fecundity in Insects—a General Relationship. Oikos 66(3):483–492.
65. Shingleton AW, Das J, Vinicius L, Stern DL, (2005) The temporal requirements for insulin signaling during development in Drosophila. PLoS biology 3(9):e289. 16086608
66. DeFalco T, Camara N, Le Bras S, Van Doren M, (2008) Nonautonomous sex determination controls sexually dimorphic development of the Drosophila gonad. Developmental cell 14(2):275–286. doi: 10.1016/j.devcel.2007.12.005 18267095
67. Keisman EL, Baker BS, (2001) The Drosophila sex determination hierarchy modulates wingless and decapentaplegic signaling to deploy dachshund sex-specifically in the genital imaginal disc. Development 128(9):1643–1656. 11290302
68. Ahmad SM, Baker BS, (2002) Sex-specific deployment of FGF signaling in Drosophila recruits mesodermal cells into the male genital imaginal disc. Cell 109(5):651–661. 12062107
69. Steinmann-Zwicky M, Schmid H, Nothiger R, (1989) Cell-autonomous and inductive signals can determine the sex of the germ line of drosophila by regulating the gene Sxl. Cell 57(1):157–166. 2702687
70. Okamoto N, et al. (2013) A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila. Genes & development 27(1):87–97.
71. Honegger B, et al. (2008) Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance. Journal of biology 7(3):10. doi: 10.1186/jbiol72 18412985
72. Gronke S, Clarke DF, Broughton S, Andrews TD, Partridge L, (2010) Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS genetics 6(2):e1000857. doi: 10.1371/journal.pgen.1000857 20195512
73. Bohni R, et al. (1999) Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97(7):865–875. 10399915
74. Chen C, Jack J, Garofalo RS, (1996) The Drosophila insulin receptor is required for normal growth. Endocrinology 137(3):846–856. 8603594
75. Long JC, Caceres JF, (2009) The SR protein family of splicing factors: master regulators of gene expression. The Biochemical journal 417(1):15–27. doi: 10.1042/BJ20081501 19061484
76. Zhong XY, Wang P, Han J, Rosenfeld MG, Fu XD, (2009) SR proteins in vertical integration of gene expression from transcription to RNA processing to translation. Molecular cell 35(1):1–10. doi: 10.1016/j.molcel.2009.06.016 19595711
77. Shepard PJ, Hertel KJ, (2009) The SR protein family. Genome biology 10(10):242. doi: 10.1186/gb-2009-10-10-242 19857271
78. Sano H, et al. (2015) The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster. PLoS Genet. 11(5): e1005209. doi: 10.1371/journal.pgen.1005209 26020940
79. Bai H, Kang P, Hernandez AM, Tatar M, (2013) Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila. PLoS genetics 9(11):e1003941. doi: 10.1371/journal.pgen.1003941 24244197
80. Bai H, Kang P, Tatar M, (2012) Drosophila insulin-like peptide-6 (dilp6) expression from fat body extends lifespan and represses secretion of Drosophila insulin-like peptide-2 from the brain. Aging cell 11(6):978–985. doi: 10.1111/acel.12000 22935001
81. Nassel DR, Kubrak OI, Liu Y, Luo J, Lushchak OV, (2013) Factors that regulate insulin producing cells and their output in Drosophila. Frontiers in physiology 4:252. doi: 10.3389/fphys.2013.00252 24062693
82. Delanoue R, Slaidina M, Leopold P, (2010) The steroid hormone ecdysone controls systemic growth by repressing dMyc function in Drosophila fat cells. Developmental cell 18(6):1012–1021. doi: 10.1016/j.devcel.2010.05.007 20627082
83. Rideout EJ, Marshall L, Grewal SS, (2012) Drosophila RNA polymerase III repressor Maf1 controls body size and developmental timing by modulating tRNAiMet synthesis and systemic insulin signaling. Proceedings of the National Academy of Sciences of the United States of America 109(4):1139–1144. doi: 10.1073/pnas.1113311109 22228302
84. Sanchez L, Gorfinkiel N, Guerrero I, (2001) Sex determination genes control the development of the Drosophila genital disc, modulating the response to Hedgehog, Wingless and Decapentaplegic signals. Development 128(7):1033–1043. 11245569
85. DeFalco TJ, et al. (2003) Sex-specific apoptosis regulates sexual dimorphism in the Drosophila embryonic gonad. Developmental cell 5(2):205–216. 12919673
86. Taylor BJ, Truman JW, (1992) Commitment of abdominal neuroblasts in Drosophila to a male or female fate is dependent on genes of the sex-determining hierarchy. Development 114(3):625–642. 1618132
87. Birkholz O, Rickert C, Berger C, Urbach R, Technau GM, (2013) Neuroblast pattern and identity in the Drosophila tail region and role of doublesex in the survival of sex-specific precursors. Development 140(8):1830–1842. doi: 10.1242/dev.090043 23533181
88. Gotoh H, et al. (2014) Developmental link between sex and nutrition; doublesex regulates sex-specific mandible growth via juvenile hormone signaling in stag beetles. PLoS genetics 10(1):e1004098. doi: 10.1371/journal.pgen.1004098 24453990
89. Clough E, et al. (2014) Sex- and tissue-specific functions of Drosophila doublesex transcription factor target genes. Developmental cell 31(6):761–773. doi: 10.1016/j.devcel.2014.11.021 25535918
90. Taylor K, Kimbrell DA, (2007) Host immune response and differential survival of the sexes in Drosophila. Fly 1(4):197–204. 18820477
91. Neckameyer WS, Matsuo H, (2008) Distinct neural circuits reflect sex, sexual maturity, and reproductive status in response to stress in Drosophila melanogaster. Neuroscience 156(4):841–856. doi: 10.1016/j.neuroscience.2008.08.020 18790015
92. Neckameyer WS, Weinstein JS, (2005) Stress affects dopaminergic signaling pathways in Drosophila melanogaster. Stress 8(2):117–131. 16019603
93. Tower J, (2006) Sex-specific regulation of aging and apoptosis. Mechanisms of ageing and development 127(9):705–718. 16764907
94. Magwere T, Chapman T, Partridge L, (2004) Sex differences in the effect of dietary restriction on life span and mortality rates in female and male Drosophila melanogaster. The journals of gerontology. Series A, Biological sciences and medical sciences 59(1):3–9.
95. Lin YJ, Seroude L, Benzer S, (1998) Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282(5390):943–946. 9794765
96. Clancy DJ, et al. (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292(5514):104–106. 11292874
97. Broughton SJ, et al. (2005) Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proceedings of the National Academy of Sciences of the United States of America 102(8):3105–3110. 15708981
98. DiAngelo JR, Bland ML, Bambina S, Cherry S, Birnbaum MJ, (2009) The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling. Proceedings of the National Academy of Sciences of the United States of America 106(49):20853–20858. doi: 10.1073/pnas.0906749106 19861550
99. Karpac J, Younger A, Jasper H, (2011) Dynamic coordination of innate immune signaling and insulin signaling regulates systemic responses to localized DNA damage. Developmental cell 20(6):841–854. doi: 10.1016/j.devcel.2011.05.011 21664581
100. Teleman AA, (2010) Molecular mechanisms of metabolic regulation by insulin in Drosophila. The Biochemical journal 425(1):13–26.
101. Sun T, et al. (2014) Sexually dimorphic RB inactivation underlies mesenchymal glioblastoma prevalence in males. The Journal of clinical investigation 124(9):4123–4133. doi: 10.1172/JCI71048 25083989
102. Wild S, Roglic G, Green A, Sicree R, King H, (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes care 27(5):1047–1053. 15111519
103. Marshall L, Rideout EJ, Grewal SS, (2012) Nutrient/TOR-dependent regulation of RNA polymerase III controls tissue and organismal growth in Drosophila. The EMBO journal 31(8):1916–1930. doi: 10.1038/emboj.2012.33 22367393