1932

Abstract

Male and female brains display anatomical and functional differences. Such differences are observed in species across the animal kingdom, including humans, but have been particularly well-studied in two classic animal model systems, the fruit fly and the nematode . Here we summarize recent advances in understanding how the worm and fly brain acquire sexually dimorphic features during development. We highlight the advantages of each system, illustrating how the precise anatomical delineation of sexual dimorphisms in worms has enabled recent analysis into how these dimorphisms become specified during development, and how focusing on sexually dimorphic neurons in the fly has enabled an increasingly detailed understanding of sex-specific behaviors.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cellbio-120319-115237
2021-10-06
2024-04-30
Loading full text...

Full text loading...

/deliver/fulltext/cellbio/37/1/annurev-cellbio-120319-115237.html?itemId=/content/journals/10.1146/annurev-cellbio-120319-115237&mimeType=html&fmt=ahah

Literature Cited

  1. Abreu AP, Dauber A, Macedo DB, Noel SD, Brito VN et al. 2013. Central precocious puberty caused by mutations in the imprinted gene MKRN3. N. Engl. J. Med. 368:2467–75
    [Google Scholar]
  2. Aeschimann F, Kumari P, Bartake H, Gaidatzis D, Xu L et al. 2017. LIN41 post-transcriptionally silences mRNAs by two distinct and position-dependent mechanisms. Mol. Cell 65:476–89.e4
    [Google Scholar]
  3. Anand A, Villella A, Ryner LC, Carlo T, Goodwin SF et al. 2001. Molecular genetic dissection of the sex-specific and vital functions of the Drosophila melanogaster sex determination gene fruitless. Genetics 158:1569–95
    [Google Scholar]
  4. Arbeitman MN, Fleming AA, Siegal ML, Null BH, Baker BS. 2004. A genomic analysis of Drosophila somatic sexual differentiation and its regulation. Development 131:2007–21
    [Google Scholar]
  5. Arbeitman MN, New FN, Fear JM, Howard TS, Dalton JE, Graze RM 2016. Sex differences in Drosophila somatic gene expression: variation and regulation by doublesex. G3 6:1799–808
    [Google Scholar]
  6. Arnold AP. 2020. Sexual differentiation of brain and other tissues: five questions for the next 50 years. Horm. Behav 120:104691
    [Google Scholar]
  7. Asahina K. 2017. Neuromodulation and strategic action choice in Drosophila aggression. Annu. Rev. Neurosci. 40:51–75
    [Google Scholar]
  8. Asahina K. 2018. Sex differences in Drosophila behavior: qualitative and quantitative dimorphism. Curr. Opin. Physiol. 6:35–45
    [Google Scholar]
  9. Auer TO, Benton R. 2016. Sexual circuitry in Drosophila. Curr. Opin. Neurobiol. 38:18–26
    [Google Scholar]
  10. Avendano MS, Vazquez MJ, Tena-Sempere M. 2017. Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty. Hum. Reprod. Update 23:737–63
    [Google Scholar]
  11. Baker BS, Wolfner MF. 1988. A molecular analysis of doublesex, a bifunctional gene that controls both male and female sexual differentiation in Drosophila melanogaster. Genes Dev 2:477–89
    [Google Scholar]
  12. Barr MM, García LR. 2006. Male mating behavior. WormBook https://doi.org/10.1895/wormbook.1.78.1
    [Crossref] [Google Scholar]
  13. Barr MM, García LR, Portman DS. 2018. Sexual dimorphism and sex differences in Caenorhabditis elegans neuronal development and behavior. Genetics 208:909–35
    [Google Scholar]
  14. Barrios A, Ghosh R, Fang C, Emmons SW, Barr MM. 2012. PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans. Nat. Neurosci. 15:1675–82
    [Google Scholar]
  15. Barrios A, Nurrish S, Emmons SW. 2008. Sensory regulation of C. elegans male mate-searching behavior. Curr. Biol. 18:1865–71
    [Google Scholar]
  16. Bayer EA, Stecky RC, Neal L, Katsamba PS, Ahlsen G et al. 2020a. Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior. eLife 9:e59614
    [Google Scholar]
  17. Bayer EA, Sun H, Rafi I, Hobert O. 2020b. Temporal, spatial, sexual and environmental regulation of the master regulator of sexual differentiation in C. elegans. Curr. Biol. 30:3604–16.e3
    [Google Scholar]
  18. Bell LR, Horabin JI, Schedl P, Cline TW. 1991. Positive autoregulation of Sex-lethal by alternative splicing maintains the female determined state in Drosophila. Cell 65:229–39
    [Google Scholar]
  19. Belote JM, McKeown M, Boggs RT, Ohkawa R, Sosnowski BA. 1989. Molecular genetics of transformer, a genetic switch controlling sexual differentiation in Drosophila. Dev. Genet. 10:143–54
    [Google Scholar]
  20. Berghoff E, Glenwinkel L, Bhattacharya A, Sun H, Mohammadi Net al 2021. The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons. eLife 10:e64903
    [Google Scholar]
  21. Berkseth M, Ikegami K, Arur S, Lieb JD, Zarkower D 2013. TRA-1 ChIP-seq reveals regulators of sexual differentiation and multilevel feedback in nematode sex determination. PNAS 110:16033–38
    [Google Scholar]
  22. Bettinger JC, Euling S, Rougvie AE. 1997. The terminal differentiation factor LIN-29 is required for proper vulval morphogenesis and egg laying in Caenorhabditis elegans. Development 124:4333–42
    [Google Scholar]
  23. Billeter J-C, Goodwin SF. 2004. Characterization of Drosophila fruitless-gal4 transgenes reveals expression in male-specific fruitless neurons and innervation of male reproductive structures. J. Comp. Neurol 475:270–87
    [Google Scholar]
  24. Billeter J-C, Rideout EJ, Dornan AJ, Goodwin SF. 2006a. Control of male sexual behavior in Drosophila by the sex determination pathway. Curr. Biol. 16:R766–76
    [Google Scholar]
  25. Billeter J-C, Villella A, Allendorfer JB, Dornan AJ, Richardson M et al. 2006b. Isoform-specific control of male neuronal differentiation and behavior in Drosophila by the fruitless gene. Curr. Biol. 16:1063–76
    [Google Scholar]
  26. Billeter J-C, Wolfner MF. 2018. Chemical cues that guide female reproduction in Drosophila melanogaster. J. Chem. Ecol. 44:750–69
    [Google Scholar]
  27. 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 140:1830–42
    [Google Scholar]
  28. 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 50:739–47
    [Google Scholar]
  29. Bogovic JA, Otsuna H, Heinrich L, Ito M, Jeter J et al. 2020. An unbiased template of the Drosophila brain and ventral nerve cord. PLOS ONE 15:e0236495
    [Google Scholar]
  30. Bridges CB. 1921. Triploid intersexes in Drosophila melanogaster. Science 54:252–54
    [Google Scholar]
  31. Brovkina MV, Duffié R, Burtis AEC, Clowney EJ. 2021. Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization. PLOS Genet 17:e1009338
    [Google Scholar]
  32. Burtis KC, Baker BS. 1989. Drosophila doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell 56:997–1010
    [Google Scholar]
  33. Burtis KC, Coschigano KT, Baker BS, Wensink PC. 1991. The doublesex proteins of Drosophila melanogaster bind directly to a sex-specific yolk protein gene enhancer. EMBO J 10:2577–82
    [Google Scholar]
  34. Bussell JJ, Yapici N, Zhang SX, Dickson BJ, Vosshall LB. 2014. Abdominal-B neurons control Drosophila virgin female receptivity. Curr. Biol. 24:1584–95
    [Google Scholar]
  35. Cachero S, Ostrovsky AD, Yu JY, Dickson BJ, Jefferis GS. 2010. Sexual dimorphism in the fly brain. Curr. Biol. 20:1589–601
    [Google Scholar]
  36. Chaharbakhshi E, Jemc JC. 2016. Broad-complex, tramtrack, and bric-a-brac (BTB) proteins: critical regulators of development. Genesis 54:505–18
    [Google Scholar]
  37. Chawla G, Sokol NS. 2012. Hormonal activation of let-7-C microRNAs via EcR is required for adult Drosophila melanogaster morphology and function. Development 139:1788–97
    [Google Scholar]
  38. Cline TW, Meyer BJ. 1996. Vive la difference: males versus females in flies versus worms. Annu. Rev. Genet. 30:637–702
    [Google Scholar]
  39. Clough E, Jimenez E, Kim YA, Whitworth C, Neville MC et al. 2014. Sex- and tissue-specific functions of Drosophila Doublesex transcription factor target genes. Dev. Cell 31:761–73
    [Google Scholar]
  40. Clough E, Oliver B. 2012. Genomics of sex determination in Drosophila. Brief. Funct. Genom 11:387–94
    [Google Scholar]
  41. Collins KM, Bode A, Fernandez RW, Tanis JE, Brewer JC et al. 2016. Activity of the C. elegans egg-laying behavior circuit is controlled by competing activation and feedback inhibition. eLife 5:e21126
    [Google Scholar]
  42. Conradt B, Horvitz HR. 1999. The TRA-1A sex determination protein of C. elegans regulates sexually dimorphic cell deaths by repressing the egl-1 cell death activator gene. Cell 98:317–27
    [Google Scholar]
  43. Cook SJ, Jarrell TA, Brittin CA, Wang Y, Bloniarz AE et al. 2019. Whole-animal connectomes of both Caenorhabditis elegans sexes. Nature 571:63–71
    [Google Scholar]
  44. Coschigano KT, Wensink PC. 1993. Sex-specific transcriptional regulation by the male and female doublesex proteins of Drosophila. Genes Dev 7:42–54
    [Google Scholar]
  45. Crickmore MA, Vosshall LB. 2013. Opposing dopaminergic and GABAergic neurons control the duration and persistence of copulation in Drosophila. Cell 155:881–93
    [Google Scholar]
  46. Cury KM, Prud'homme B, Gompel N 2019. A short guide to insect oviposition: when, where and how to lay an egg. J. Neurogenet. 33:75–89
    [Google Scholar]
  47. Dalton JE, Fear JM, Knott S, Baker BS, McIntyre LM, Arbeitman MN. 2013. Male-specific Fruitless isoforms have different regulatory roles conferred by distinct zinc finger DNA binding domains. BMC Genom 14:659
    [Google Scholar]
  48. Darlington C. 2017. The Female Brain Boca Raton, FL: CRC Press, 2nd ed..
  49. Desai C, Garriga G, McIntire SL, Horvitz HR. 1988. A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons. Nature 336:638–46
    [Google Scholar]
  50. Deutsch D, Clemens J, Thiberge SY, Guan G, Murthy M. 2019. Shared song detector neurons in Drosophila male and female brains drive sex-specific behaviors. Curr. Biol. 29:3200–15.e5
    [Google Scholar]
  51. Emmons SW. 2018. Neural circuits of sexual behavior in Caenorhabditis elegans. Annu. Rev. Neurosci. 41:349–69
    [Google Scholar]
  52. Erdman SE, Burtis KC. 1993. The Drosophila doublesex proteins share a novel zinc finger related DNA binding domain. EMBO J 12:527–35
    [Google Scholar]
  53. Erickson JW, Quintero JJ. 2007. Indirect effects of ploidy suggest X chromosome dose, not the X:A ratio, signals sex in Drosophila. PLOS Biol 5:e332
    [Google Scholar]
  54. Fagegaltier D, Konig A, Gordon A, Lai EC, Gingeras TR et al. 2014. A genome-wide survey of sexually dimorphic expression of Drosophila miRNAs identifies the steroid hormone-induced miRNA let-7 as a regulator of sexual identity. Genetics 198:647–68
    [Google Scholar]
  55. Fairbairn DJ. 2013. Odd Couples: Extraordinary Differences Between the Sexes in the Animal Kingdom Princeton, NJ: Princeton Univ. Press
  56. Feinberg EH, Vanhoven MK, Bendesky A, Wang G, Fetter RD et al. 2008. GFP Reconstitution Across Synaptic Partners (GRASP) defines cell contacts and synapses in living nervous systems. Neuron 57:353–63
    [Google Scholar]
  57. Feng K, Palfreyman MT, Hasemeyer M, Talsma A, Dickson BJ. 2014. Ascending SAG neurons control sexual receptivity of Drosophila females. Neuron 83:135–48
    [Google Scholar]
  58. Fernandez RW, Wei K, Wang EY, Mikalauskaite D, Olson A et al. 2020. Cellular expression and functional roles of all 26 neurotransmitter GPCRs in the C. elegans egg-laying circuit. J. Neurosci. 40:7475–88
    [Google Scholar]
  59. García LR. 2014. Regulation of sensory motor circuits used in C. elegans male intromission behavior. Semin. Cell Dev. Biol. 33:42–49
    [Google Scholar]
  60. García LR, Portman DS. 2016. Neural circuits for sexually dimorphic and sexually divergent behaviors in Caenorhabditis elegans. Curr. Opin. Neurobiol. 38:46–52
    [Google Scholar]
  61. Garner SRC, Castellanos MC, Baillie KE, Lian T, Allan DW 2018. Drosophila female-specific Ilp7 motoneurons are generated by Fruitless-dependent cell death in males and by a double-assurance survival role for Transformer in females. Development 145:dev150821
    [Google Scholar]
  62. Gegenhuber B, Tollkuhn J. 2020. Signatures of sex: sex differences in gene expression in the vertebrate brain. Wiley Interdiscip. Rev. Dev. Biol 9:e348
    [Google Scholar]
  63. Ghosh N, Bakshi A, Khandelwal R, Rajan SG, Joshi R. 2019. The Hox gene Abdominal-B uses DoublesexF as a cofactor to promote neuroblast apoptosis in the Drosophila central nervous system. Development 146:dev175158
    [Google Scholar]
  64. Goldman TD, Arbeitman MN. 2007. Genomic and functional studies of Drosophila sex hierarchy regulated gene expression in adult head and nervous system tissues. PLOS Genet 3:e216
    [Google Scholar]
  65. Gotoh H, Miyakawa H, Ishikawa A, Ishikawa Y, Sugime Y et al. 2014. Developmental link between sex and nutrition; doublesex regulates sex-specific mandible growth via juvenile hormone signaling in stag beetles. PLOS Genet 10:e1004098
    [Google Scholar]
  66. Gray JM, Hill JJ, Bargmann CI 2005. A circuit for navigation in Caenorhabditis elegans. PNAS 102:3184–91
    [Google Scholar]
  67. Hasemeyer M, Yapici N, Heberlein U, Dickson BJ. 2009. Sensory neurons in the Drosophila genital tract regulate female reproductive behavior. Neuron 61:511–18
    [Google Scholar]
  68. Hedley ML, Maniatis T. 1991. Sex-specific splicing and polyadenylation of dsx pre-mRNA requires a sequence that binds specifically to tra-2 protein in vitro. Cell 65:579–86
    [Google Scholar]
  69. Heinrichs V, Ryner LC, Baker BS. 1998. Regulation of sex-specific selection of fruitless 5' splice sites by transformer and transformer-2. Mol. Cell Biol. 18:450–58
    [Google Scholar]
  70. Hill RC, de Carvalho CE, Salogiannis J, Schlager B, Pilgrim D, Haag ES. 2006. Genetic flexibility in the convergent evolution of hermaphroditism in Caenorhabditis nematodes. Dev. Cell 10:531–38
    [Google Scholar]
  71. Hilliard MA, Bargmann CI, Bazzicalupo P. 2002. C. elegans responds to chemical repellents by integrating sensory inputs from the head and the tail. Curr. Biol. 12:730–34
    [Google Scholar]
  72. Hobert O, Kratsios P. 2019. Neuronal identity control by terminal selectors in worms, flies, and chordates. Curr. Opin. Neurobiol. 56:97–105
    [Google Scholar]
  73. Hodgkin J. 1987. A genetic analysis of the sex-determining gene, tra-1, in the nematode Caenorhabditis elegans. Genes Dev 1:731–45
    [Google Scholar]
  74. Hodgkin JA, Brenner S. 1977. Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans. Genetics 86:275–87
    [Google Scholar]
  75. Hoshijima K, Inoue K, Higuchi I, Sakamoto H, Shimura Y. 1991. Control of doublesex alternative splicing by transformer and transformer-2 in Drosophila. Science 252:833–36
    [Google Scholar]
  76. 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. PNAS 89:8092–96
    [Google Scholar]
  77. 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 344:461–63
    [Google Scholar]
  78. Ishii K, Wohl M, DeSouza A, Asahina K 2020. Sex-determining genes distinctly regulate courtship capability and target preference via sexually dimorphic neurons. eLife 9:e52701
    [Google Scholar]
  79. Ito H, Fujitani K, Usui K, Shimizu-Nishikawa K, Tanaka S, Yamamoto D 1996. Sexual orientation in Drosophila is altered by the satori mutation in the sex-determination gene fruitless that encodes a zinc finger protein with a BTB domain. PNAS 93:9687–92
    [Google Scholar]
  80. Ito H, Sato K, Koganezawa M, Ote M, Matsumoto K et al. 2012. Fruitless recruits two antagonistic chromatin factors to establish single-neuron sexual dimorphism. Cell 149:1327–38
    [Google Scholar]
  81. Ito H, Sato K, Kondo S, Ueda R, Yamamoto D. 2016. Fruitless represses robo1 transcription to shape male-specific neural morphology and behavior in Drosophila. Curr. Biol. 26:1532–42
    [Google Scholar]
  82. Jarrell TA, Wang Y, Bloniarz AE, Brittin CA, Xu M et al. 2012. The connectome of a decision-making neural network. Science 337:437–44
    [Google Scholar]
  83. Jazin E, Cahill L. 2010. Sex differences in molecular neuroscience: from fruit flies to humans. Nat. Rev. Neurosci. 11:9–17
    [Google Scholar]
  84. Jois S, Chan YB, Fernandez MP, Leung AK-W. 2018. Characterization of the sexually dimorphic fruitless neurons that regulate copulation duration. Front. Physiol. 9:780
    [Google Scholar]
  85. Kijimoto T, Moczek AP, Andrews J 2012. Diversification of doublesex function underlies morph-, sex-, and species-specific development of beetle horns. PNAS 109:20526–31
    [Google Scholar]
  86. Kimura K, Hachiya T, Koganezawa M, Tazawa T, Yamamoto D. 2008. Fruitless and doublesex coordinate to generate male-specific neurons that can initiate courtship. Neuron 59:759–69
    [Google Scholar]
  87. Kimura K, Sato C, Koganezawa M, Yamamoto D. 2015. Drosophila ovipositor extension in mating behavior and egg deposition involves distinct sets of brain interneurons. PLOS ONE 10:e0126445
    [Google Scholar]
  88. Kopp A. 2012. Dmrt genes in the development and evolution of sexual dimorphism. Trends Genet 28:175–84
    [Google Scholar]
  89. Kopp A, Duncan I, Godt D, Carroll SB. 2000. Genetic control and evolution of sexually dimorphic characters in Drosophila. Nature 408:553–59
    [Google Scholar]
  90. Kucherenko MM, Barth J, Fiala A, Shcherbata HR. 2012. Steroid-induced microRNA let-7 acts as a spatio-temporal code for neuronal cell fate in the developing Drosophila brain. EMBO J 31:4511–23
    [Google Scholar]
  91. L'Hernault SW 2006. Spermatogenesis. WormBook https://doi.org/10.1895/wormbook.1.85.1
    [Crossref] [Google Scholar]
  92. Lawson H, Vuong E, Miller RM, Kiontke K, Fitch DH Portman DS. 2019. The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system. eLife 8:e43660
    [Google Scholar]
  93. Lawson H, Wexler LR, Wnuk HK, Portman DS. 2020. Dynamic, non-binary specification of sexual state in the C. elegans nervous system. Curr. Biol. 30:3617–23.e3
    [Google Scholar]
  94. Lebo MS, Sanders LE, Sun F, Arbeitman MN. 2009. Somatic, germline and sex hierarchy regulated gene expression during Drosophila metamorphosis. BMC Genom 10:80
    [Google Scholar]
  95. Lee G, Foss M, Goodwin SF, Carlo T, Taylor BJ, Hall JC 2000. Spatial, temporal, and sexually dimorphic expression patterns of the fruitless gene in the Drosophila central nervous system. J. Neurobiol. 43:404–26
    [Google Scholar]
  96. Lee G, Hall JC, Park JH. 2002. Doublesex gene expression in the central nervous system of Drosophila melanogaster. J. Neurogenet. 16:229–48
    [Google Scholar]
  97. Lee KM, Daubnerová I, Isaac RE, Zhang C, Choi S et al. 2015. A neuronal pathway that controls sperm ejection and storage in female Drosophila. Curr. Biol. 25:790–97
    [Google Scholar]
  98. Lee SS, Wu MN. 2020. Neural circuit mechanisms encoding motivational states in Drosophila. Curr. Opin. Neurobiol. 64:135–42
    [Google Scholar]
  99. Lee T. 2017. Wiring the Drosophila brain with individually tailored neural lineages. Curr. Biol. 27:R77–82
    [Google Scholar]
  100. Leighton DH, Sternberg PW. 2016. Mating pheromones of Nematoda: olfactory signaling with physiological consequences. Curr. Opin. Neurobiol. 38:119–24
    [Google Scholar]
  101. Li X, Ishimoto H, Kamikouchi A 2018. Auditory experience controls the maturation of song discrimination and sexual response in Drosophila. eLife 7:e34348
    [Google Scholar]
  102. Lin H-H, Cao D-S, Sethi S, Zeng Z, Chin JSR et al. 2016. Hormonal modulation of pheromone detection enhances male courtship success. Neuron 90:1272–85
    [Google Scholar]
  103. Lints R, Emmons SW. 2002. Regulation of sex-specific differentiation and mating behavior in C. elegans by a new member of the DM domain transcription factor family. Genes Dev 16:2390–402
    [Google Scholar]
  104. Lipton J, Kleemann G, Ghosh R, Lints R, Emmons SW. 2004. Mate searching in Caenorhabditis elegans: a genetic model for sex drive in a simple invertebrate. J. Neurosci. 24:7427–34
    [Google Scholar]
  105. Liu KS, Sternberg PW. 1995. Sensory regulation of male mating behavior in Caenorhabditis elegans. Neuron 14:79–89
    [Google Scholar]
  106. Liu W, Ganguly A, Huang J, Wang Y, Ni JD et al. 2019. Neuropeptide F regulates courtship in Drosophila through a male-specific neuronal circuit. eLife 8:e49574
    [Google Scholar]
  107. Luo SD, Baker BS 2015. Constraints on the evolution of a doublesex target gene arising from doublesex's pleiotropic deployment. PNAS 112:E852–61
    [Google Scholar]
  108. Luo SD, Shi GW, Baker BS. 2011. Direct targets of the D. melanogaster DSXF protein and the evolution of sexual development. Development 138:2761–71
    [Google Scholar]
  109. Mason DA, Rabinowitz JS, Portman DS 2008. dmd-3, a doublesex-related gene regulated by tra-1, governs sex-specific morphogenesis in C. elegans. Development 135:2373–82
    [Google Scholar]
  110. Masuzzo A, Maniere G, Viallat-Lieutaud A, Avazeri E, Zugasti O et al. 2019. Peptidoglycan-dependent NF-κB activation in a small subset of brain octopaminergic neurons controls female oviposition. eLife 8:e50559
    [Google Scholar]
  111. Matson CK, Zarkower D. 2012. Sex and the singular DM domain: insights into sexual regulation, evolution and plasticity. Nat. Rev. Genet. 13:163–74
    [Google Scholar]
  112. McCarthy MM, Arnold AP. 2011. Reframing sexual differentiation of the brain. Nat. Neurosci. 14:677–83
    [Google Scholar]
  113. Meinertzhagen IA. 2018. Of what use is connectomics? A personal perspective on the Drosophila connectome. J. Exp. Biol. 221:jeb164954
    [Google Scholar]
  114. Meissner GW, Luo SD, Dias BG, Texada MJ, Baker BS 2016. Sex-specific regulation of Lgr3 in Drosophila neurons. PNAS 113:E1256–65
    [Google Scholar]
  115. Mellert DJ, Knapp J-M, Manoli DS, Meissner GW, Baker BS. 2010. Midline crossing by gustatory receptor neuron axons is regulated by fruitless, doublesex and the Roundabout receptors. Development 137:323–32
    [Google Scholar]
  116. Mezzera C, Brotas M, Gaspar M, Pavlou HJ, Goodwin SF, Vasconcelos ML. 2020. Ovipositor extrusion promotes the transition from courtship to copulation and signals female acceptance in Drosophila melanogaster. Curr. Biol. 30:3736–48.e5
    [Google Scholar]
  117. Molina-García L, Lloret-Fernández C, Cook SJ, Kim B, Bonnington RC et al. 2020. Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating. eLife 9:e48361
    [Google Scholar]
  118. Moss EG, Romer-Seibert J. 2014. Cell-intrinsic timing in animal development. Wiley Interdiscip. Rev. Dev. Biol 3:365–77
    [Google Scholar]
  119. Mowrey WR, Bennett JR, Portman DS. 2014. Distributed effects of biological sex define sex-typical motor behavior in Caenorhabditis elegans. J. Neurosci. 34:1579–91
    [Google Scholar]
  120. Naqvi S, Godfrey AK, Hughes JF, Goodheart ML, Mitchell RN, Page DC. 2019. Conservation, acquisition, and functional impact of sex-biased gene expression in mammals. Science 365:eaaw7317
    [Google Scholar]
  121. Narayan A, Venkatachalam V, Durak O, Reilly DK, Bose N et al. 2016. Contrasting responses within a single neuron class enable sex-specific attraction in Caenorhabditis elegans. PNAS 113:E1392–1401
    [Google Scholar]
  122. Neville MC, Nojima T, Ashley E, Parker DJ, Walker J et al. 2014. Male-specific fruitless isoforms target neurodevelopmental genes to specify a sexually dimorphic nervous system. Curr. Biol. 24:229–41
    [Google Scholar]
  123. Newell NR, New FN, Dalton JE, McIntyre LM, Arbeitman MN 2016. Neurons that underlie Drosophila melanogaster reproductive behaviors: detection of a large male-bias in gene expression in fruitless-expressing neurons. G3 6:2455–65
    [Google Scholar]
  124. Ng R, Salem SS, Wu ST, Wu M, Lin HH et al. 2019. Amplification of Drosophila olfactory responses by a DEG/ENaC channel. Neuron 104:947–59.e5
    [Google Scholar]
  125. Nojima T, Neville MC, Goodwin SF. 2014. Fruitless isoforms and target genes specify the sexually dimorphic nervous system underlying Drosophila reproductive behavior. Fly 8:95–100
    [Google Scholar]
  126. Nojima T, Rings A, Allen AM, Otto N, Verschut TA et al. 2021. A sex-specific switch between visual and olfactory inputs underlies adaptive sex differences in behavior. Curr. Biol. 31:1175–91.e6
    [Google Scholar]
  127. Oren-Suissa M, Bayer EA, Hobert O 2016. Sex-specific pruning of neuronal synapses in Caenorhabditis elegans. Nature 533:206–11
    [Google Scholar]
  128. Pan Y, Baker BS. 2014. Genetic identification and separation of innate and experience-dependent courtship behaviors in Drosophila. Cell 156:236–48
    [Google Scholar]
  129. Pan Y, Robinett CC, Baker BS. 2011. Turning males on: activation of male courtship behavior in Drosophila melanogaster. PLOS ONE 6:e21144
    [Google Scholar]
  130. Papp A, Rougvie AE, Ambros V 1991. Molecular cloning of lin-29, a heterochronic gene required for the differentiation of hypodermal cells and the cessation of molting in C.elegans. Nucleic Acids Res 19:623–30
    [Google Scholar]
  131. Pavlou HJ, Lin AC, Neville MC, Nojima T, Diao F et al. 2016. Neural circuitry coordinating male copulation. eLife 5:e20713
    [Google Scholar]
  132. Pereira L, Aeschimann F, Wang C, Lawson H, Serrano-Saiz E et al. 2019. Timing mechanism of sexually dimorphic nervous system differentiation. eLife 8:e42078
    [Google Scholar]
  133. Pereira L, Kratsios P, Serrano-Saiz E, Sheftel H, Mayo AE et al. 2015. A cellular and regulatory map of the cholinergic nervous system of C. elegans. eLife 4:e12432
    [Google Scholar]
  134. Portman DS. 2017. Sexual modulation of sex-shared neurons and circuits in Caenorhabditis elegans. J. Neurosci. Res. 95:527–38
    [Google Scholar]
  135. Ren Q, Awasaki T, Huang Y-F, Liu Z, Lee T. 2016. Cell class-lineage analysis reveals sexually dimorphic lineage compositions in the Drosophila brain. Curr. Biol. 26:2583–93
    [Google Scholar]
  136. Rezával C, Nojima T, Neville MC, Lin AC, Goodwin SF. 2014. Sexually dimorphic octopaminergic neurons modulate female postmating behaviors in Drosophila. Curr. Biol. 24:725–30
    [Google Scholar]
  137. Rezával C, Pavlou HJ, Dornan AJ, Chan Y-B, Kravitz EA, Goodwin SF. 2012. Neural circuitry underlying Drosophila female postmating behavioral responses. Curr. Biol. 22:1155–65
    [Google Scholar]
  138. Rice GR, Barmina O, Luecke D, Hu K, Arbeitman M, Kopp A. 2019. Modular tissue-specific regulation of doublesex underpins sexually dimorphic development in Drosophila. Development 146:dev178285
    [Google Scholar]
  139. Rideout EJ, Billeter J-C, Goodwin SF. 2007. The sex-determination genes fruitless and doublesex specify a neural substrate required for courtship song. Curr. Biol. 17:1473–78
    [Google Scholar]
  140. Rideout EJ, Dornan AJ, Neville MC, Eadie S, Goodwin SF 2010. Control of sexual differentiation and behavior by the doublesex gene in Drosophila melanogaster. Nat. Neurosci. 13:458–66
    [Google Scholar]
  141. Robinett CC, Vaughan AG, Knapp JM, Baker BS. 2010. Sex and the single cell. II. There is a time and place for sex. PLOS Biol 8:e1000365
    [Google Scholar]
  142. Rougvie AE, Moss EG. 2013. Developmental transitions in C. elegans larval stages. Curr. Top. Dev. Biol. 105:153–80
    [Google Scholar]
  143. Ryner LC, Baker BS. 1991. Regulation of doublesex pre-mRNA processing occurs by 3′-splice site activation. Genes Dev 5:2071–85
    [Google Scholar]
  144. Ryner LC, Goodwin SF, Castrillon DH, Anand A, Villella A et al. 1996. Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene. Cell 87:1079–89
    [Google Scholar]
  145. Salz HK, Erickson JW. 2010. Sex determination in Drosophila: the view from the top. Fly 4:60–70
    [Google Scholar]
  146. Salzberg Y, Pechuk V, Gat A, Setty H, Sela S, Oren-Suissa M. 2020. Synaptic protein degradation controls sexually dimorphic circuits through regulation of DCC/UNC-40. Curr. Biol. 30:4128–41.e5
    [Google Scholar]
  147. Sammut M, Cook SJ, Nguyen KC, Felton T, Hall DH et al. 2015. Glia-derived neurons are required for sex-specific learning in C. elegans. Nature 526:385–90
    [Google Scholar]
  148. Sanders LE, Arbeitman MN. 2008. Doublesex establishes sexual dimorphism in the Drosophila central nervous system in an isoform-dependent manner by directing cell number. Dev. Biol. 320:378–90
    [Google Scholar]
  149. Sato K, Ito H, Yamamoto D. 2020. teiresias, a Fruitless target gene encoding an immunoglobulin-superfamily transmembrane protein, is required for neuronal feminization in Drosophila. Commun. Biol. 3:598
    [Google Scholar]
  150. Sato K, Yamamoto D. 2020. The mode of action of Fruitless: Is it an easy matter to switch the sex?. Genes Brain Behav 19:e12606
    [Google Scholar]
  151. Schafer WR. 2005. Egg-laying. WormBook https://doi.org/10.1895/wormbook.1.38.1
    [Crossref] [Google Scholar]
  152. Scheffer LK, Xu CS, Januszewski M, Lu Z, Takemura SY et al. 2020. A connectome and analysis of the adult Drosophila central brain. eLife 9:e57443
    [Google Scholar]
  153. Schrodel T, Prevedel R, Aumayr K, Zimmer M, Vaziri A. 2013. Brain-wide 3D imaging of neuronal activity in Caenorhabditis elegans with sculpted light. Nat. Methods 10:1013–20
    [Google Scholar]
  154. Schwartz HT, Horvitz HR. 2007. The C. elegans protein CEH-30 protects male-specific neurons from apoptosis independently of the Bcl-2 homolog CED-9. Genes Dev 21:3181–94
    [Google Scholar]
  155. Serrano-Saiz E, Oren-Suissa M, Bayer EA, Hobert O 2017a. Sexually dimorphic differentiation of a C. elegans hub neuron is cell autonomously controlled by a conserved transcription factor. Curr. Biol. 27:199–209
    [Google Scholar]
  156. Serrano-Saiz E, Pereira L, Gendrel M, Aghayeva U, Battacharya A et al. 2017b. A neurotransmitter atlas of the Caenorhabditis elegans male nervous system reveals sexually dimorphic neurotransmitter usage. Genetics 206:1251–69
    [Google Scholar]
  157. Sethi S, Lin HH, Shepherd AK, Volkan PC, Su CY, Wang JW. 2019. Social context enhances hormonal modulation of pheromone detection in Drosophila. Curr. Biol. 29:3887–98.e4
    [Google Scholar]
  158. Shao L, Chung P, Wong A, Siwanowicz I, Kent CF et al. 2019. A neural circuit encoding the experience of copulation in female Drosophila. Neuron 102:1025–36.e6
    [Google Scholar]
  159. Shirangi TR, Dufour HD, Williams TM, Carroll SB. 2009. Rapid evolution of sex pheromone-producing enzyme expression in Drosophila. PLOS Biol 7:e1000168
    [Google Scholar]
  160. Siehr MS, Koo PK, Sherlekar AL, Bian X, Bunkers MR et al. 2011. Multiple doublesex-related genes specify critical cell fates in a C. elegans male neural circuit. PLOS ONE 6:e26811
    [Google Scholar]
  161. Siggs OM, Beutler B. 2012. The BTB-ZF transcription factors. Cell Cycle 11:3358–69
    [Google Scholar]
  162. Siwicki KK, Kravitz EA. 2009. Fruitless, doublesex and the genetics of social behavior in Drosophila melanogaster. Curr. Opin. Neurobiol. 19:200–6
    [Google Scholar]
  163. Sokol NS, Xu P, Jan Y-N, Ambros V 2008. Drosophila let-7 microRNA is required for remodeling of the neuromusculature during metamorphosis. Genes Dev 22:1591–96
    [Google Scholar]
  164. Srinivasan J, Kaplan F, Ajredini R, Zachariah C, Alborn HT et al. 2008. A blend of small molecules regulates both mating and development in Caenorhabditis elegans. Nature 454:1115–18
    [Google Scholar]
  165. Stockinger P, Kvitsiani D, Rotkopf S, Tirian L, Dickson BJ. 2005. Neural circuitry that governs Drosophila male courtship behavior. Cell 121:795–807
    [Google Scholar]
  166. Sulston JE. 1983. Neuronal cell lineages in the nematode Caenorhabditis elegans. Cold Spring Harb. Symp. Quant. Biol. 48:443–52
    [Google Scholar]
  167. Sulston JE, Albertson DG, Thomson JN. 1980. The Caenorhabditis elegans male: postembryonic development of nongonadal structures. Dev. Biol. 78:542–76
    [Google Scholar]
  168. Sulston JE, Horvitz HR. 1977. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev. Biol. 56:110–56
    [Google Scholar]
  169. Tayler TD, Pacheco DA, Hergarden AC, Murthy M, Anderson DJ 2012. A neuropeptide circuit that coordinates sperm transfer and copulation duration in Drosophila. PNAS 109:20697–702
    [Google Scholar]
  170. 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 114:625–42
    [Google Scholar]
  171. Tekieli T, Yemini E, Nejatbakhsh A, Varol E, Fernandez R et al. 2021. Visualizing the organization and differentiation of the male-specific nervous system of C. elegans. bioRxiv 438718. https://doi.org/10.1101/2021.04.06.438718
    [Crossref]
  172. Trabzuni D, Ramasamy A, Imran S, Walker R, Smith C et al. 2013. Widespread sex differences in gene expression and splicing in the adult human brain. Nat. Commun. 4:2771
    [Google Scholar]
  173. Tsalik EL, Hobert O 2003. Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans. J. Neurobiol. 56:178–97
    [Google Scholar]
  174. Usui-Aoki K, Ito H, Ui-Tei K, Takahashi K, Lukacsovich T et al. 2000. Formation of the male-specific muscle in female Drosophila by ectopic fruitless expression. Nat. Cell Biol. 2:500–6
    [Google Scholar]
  175. Verhulst EC, van de Zande L. 2015. Double nexus–Doublesex is the connecting element in sex determination. Brief. Funct. Genom 14:396–406
    [Google Scholar]
  176. Vernes SC. 2014. Genome wide identification of Fruitless targets suggests a role in upregulating genes important for neural circuit formation. Sci. Rep 4:4412
    [Google Scholar]
  177. von Philipsborn AC, Jörchel S, Tirian L, Demir E, Morita T et al. 2014. Cellular and behavioral functions of fruitless isoforms in Drosophila courtship. Curr. Biol. 24:242–51
    [Google Scholar]
  178. Von Stetina SE, Treinin M, Miller DM. 2006. The motor circuit. Int. Rev. Neurobiol. 69:125–67
    [Google Scholar]
  179. Wang F, Wang K, Forknall N, Parekh R, Dickson BJ. 2020a. Circuit and behavioral mechanisms of sexual rejection by Drosophila females. Curr. Biol. 30:3749–60.e3
    [Google Scholar]
  180. Wang F, Wang K, Forknall N, Patrick C, Yang T et al. 2020b. Neural circuitry linking mating and egg laying in Drosophila females. Nature 579:101–5
    [Google Scholar]
  181. Wang K, Wang F, Forknall N, Yang T, Patrick C et al. 2021. Neural circuit mechanisms of sexual receptivity in Drosophila females. Nature 589:577–81
    [Google Scholar]
  182. Weinberg P, Berkseth M, Zarkower D, Hobert O 2018. Sexually dimorphic unc-6/Netrin expression controls sex-specific maintenance of synaptic connectivity. Curr. Biol. 28:623–29.e3
    [Google Scholar]
  183. Wexler LR, Miller RM, Portman DS. 2020. C. elegans males integrate food signals and biological sex to modulate state-dependent chemosensation and behavioral prioritization. Curr. Biol. 30:2695–706.e4
    [Google Scholar]
  184. White JG, Southgate E, Thomson JN, Brenner S. 1986. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos. Trans. R. Soc. B 314:1–340
    [Google Scholar]
  185. Williams TM, Selegue JE, Werner T, Gompel N, Kopp A, Carroll SB. 2008. The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila. Cell 134:610–23
    [Google Scholar]
  186. Wohl M, Ishii K, Asahina K 2020. Layered roles of fruitless isoforms in specification and function of male aggression-promoting neurons in Drosophila. eLife 9:e52702
    [Google Scholar]
  187. Wu S, Guo C, Zhao H, Sun M, Chen J et al. 2019. Drosulfakinin signaling in fruitless circuitry antagonizes P1 neurons to regulate sexual arousal in Drosophila. Nat. Commun. 10:4770
    [Google Scholar]
  188. Wu YC, Chen CH, Mercer A, Sokol NS. 2012. let-7-complex microRNAs regulate the temporal identity of Drosophila mushroom body neurons via chinmo. Dev. Cell 23:202–9
    [Google Scholar]
  189. Yang CF, Shah NM. 2014. Representing sex in the brain, one module at a time. Neuron 82:261–78
    [Google Scholar]
  190. Yang CH, Rumpf S, Xiang Y, Gordon MD, Song W et al. 2009. Control of the postmating behavioral switch in Drosophila females by internal sensory neurons. Neuron 61:519–26
    [Google Scholar]
  191. Yapici N, Kim Y-J, Ribeiro C, Dickson BJ. 2008. A receptor that mediates the post-mating switch in Drosophila reproductive behaviour. Nature 451:33–37
    [Google Scholar]
  192. Yemini E, Jucikas T, Grundy LJ, Brown AE, Schafer WR. 2013. A database of Caenorhabditis elegans behavioral phenotypes. Nat. Methods 10:877–79
    [Google Scholar]
  193. Yemini E, Lin A, Nejatbakhsh A, Varol E, Sun R et al. 2021. NeuroPAL: a multicolor atlas for whole-brain neuronal identification in C. elegans. Cell 184:272–88.e1
    [Google Scholar]
  194. Yi W, Ross JM, Zarkower D. 2000. Mab-3 is a direct tra-1 target gene regulating diverse aspects of C. elegans male sexual development and behavior. Development 127:4469–80
    [Google Scholar]
  195. Yu JY, Kanai MI, Demir E, Jefferis GS, Dickson BJ. 2010. Cellular organization of the neural circuit that drives Drosophila courtship behavior. Curr. Biol. 20:1602–14
    [Google Scholar]
  196. Zarkower D, Hodgkin J. 1992. Molecular analysis of the C. elegans sex-determining gene tra-1: a gene encoding two zinc finger proteins. Cell 70:237–49
    [Google Scholar]
  197. Zhang L, Yu J, Guo X, Wei J, Liu T, Zhang W. 2020. Parallel mechanosensory pathways direct oviposition decision-making in Drosophila. Curr. Biol. 30:3075–88.e4
    [Google Scholar]
  198. Zhang M, Chung SH, Fang-Yen C, Craig C, Kerr RA et al. 2008. A self-regulating feed-forward circuit controlling C. elegans egg-laying behavior. Curr. Biol. 18:1445–55
    [Google Scholar]
  199. Zhang SX, Miner LE, Boutros CL, Rogulja D, Crickmore MA. 2018. Motivation, perception, and chance converge to make a binary decision. Neuron 99:376–88.e6
    [Google Scholar]
  200. Zhang SX, Rogulja D, Crickmore MA. 2016. Dopaminergic circuitry underlying mating drive. Neuron 91:168–81
    [Google Scholar]
  201. Zhang SX, Rogulja D, Crickmore MA. 2019. Recurrent circuitry sustains Drosophila courtship drive while priming itself for satiety. Curr. Biol. 29:3216–28.e9
    [Google Scholar]
  202. Zhang Y, Ng R, Neville MC, Goodwin SF, Su C-Y. 2020. Distinct roles and synergistic function of FruM isoforms in Drosophila olfactory receptor neurons. Cell Rep 33:108516
    [Google Scholar]
  203. Zhao S, Deanhardt B, Barlow GT, Schleske PG, Rossi AM, Volkan PC. 2020. Chromatin-based reprogramming of a courtship regulator by concurrent pheromone perception and hormone signaling. Sci. Adv. 6:eaba6913
    [Google Scholar]
  204. Zhou H, Whitworth C, Pozmanter C, Neville MC, Van Doren M. 2021. Doublesex regulates fruitless expression to promote sexual dimorphism of the gonad stem cell niche. PLOS Genet 17:e1009468
    [Google Scholar]
  205. Zhu LJ, Christensen RG, Kazemian M, Hull CJ, Enuameh MS et al. 2011. FlyFactorSurvey: a database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system. Nucleic Acids Res 39:D111–17
    [Google Scholar]
/content/journals/10.1146/annurev-cellbio-120319-115237
Loading
/content/journals/10.1146/annurev-cellbio-120319-115237
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error