Doublesex regulates fruitless expression to promote sexual dimorphism of the gonad stem cell niche
Autoři:
Hong Zhou aff001; Cale Whitworth aff001; Caitlin Pozmanter aff001; Megan C. Neville aff002; Mark Van Doren aff001
Působiště autorů:
Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD, United States of America
aff001; Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford, United Kingdom
aff002
Vyšlo v časopise:
Doublesex regulates fruitless expression to promote sexual dimorphism of the gonad stem cell niche. PLoS Genet 17(3): e1009468. doi:10.1371/journal.pgen.1009468
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009468
Souhrn
Doublesex (Dsx) and Fruitless (Fru) are the two downstream transcription factors that actuate Drosophila sex determination. While Dsx assists Fru to regulate sex-specific behavior, whether Fru collaborates with Dsx in regulating other aspects of sexual dimorphism remains unknown. One important aspect of sexual dimorphism is found in the gonad stem cell (GSC) niches, where male and female GSCs are regulated to create large numbers of sperm and eggs. Here we report that Fru is expressed male-specifically in the GSC niche and plays important roles in the development and maintenance of these cells. Unlike previously-studied aspects of sex-specific Fru expression, which are regulated by Transformer (Tra)-mediated alternative splicing, we show that male-specific expression of fru in the gonad is regulated downstream of dsx, and is independent of tra. fru genetically interacts with dsx to support maintenance of the niche throughout development. Ectopic expression of fru inhibited female niche formation and partially masculinized the ovary. fru is also required autonomously for cyst stem cell maintenance and cyst cell survival. Finally, we identified a conserved Dsx binding site upstream of fru promoter P4 that regulates fru expression in the niche, indicating that fru is likely a direct target for transcriptional regulation by Dsx. These findings demonstrate that fru acts outside the nervous system to influence sexual dimorphism and reveal a new mechanism for regulating sex-specific expression of fru that is regulated at the transcriptional level by Dsx, rather than by alternative splicing by Tra.
Klíčová slova:
Cloning – Gonads – Larvae – Ovaries – Sex determination – Sexual dimorphism – Stem cell niche – Testes
Zdroje
1. Zarkower D. Establishing sexual dimorphism: conservation amidst diversity? Nat Rev Genet 2, 175–185. (2001). doi: 10.1038/35056032 11256069
2. Crews D. Gamete production, sex hormone secretion, and mating behavior uncoupled. Horm Behav 18, 22–28. (1984). doi: 10.1016/0018-506x(84)90047-3 6538547
3. Serrano-Saiz E, Oren-Suissa M, Bayer EA, Hobert O. Sexually Dimorphic Differentiation of a C. elegans Hub Neuron Is Cell Autonomously Controlled by a Conserved Transcription Factor. Curr Biol 27, 199–209. (2017). doi: 10.1016/j.cub.2016.11.045 28065609
4. Salvemini M, Polito C, Saccone G. Fruitless alternative splicing and sex behaviour in insects: an ancient and unforgettable love story? J Genet 89, 287–299. (2010). doi: 10.1007/s12041-010-0040-z 20876995
5. Kimura K, Ote M, Tazawa T, Yamamoto D. Fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain. Nature 438, 229–233. (2005). doi: 10.1038/nature04229 16281036
6. Koganezawa M, Kimura K, Yamamoto D. The Neural Circuitry that Functions as a Switch for Courtship versus Aggression in Drosophila Males. Curr Biol 26, 1395–1403. (2016) doi: 10.1016/j.cub.2016.04.017 27185554
7. Rideout EJ, Billeter JC, Goodwin SF. The sex-determination genes fruitless and doublesex specify a neural substrate required for courtship song. Curr Biol 17, 1473–1478. (2007). doi: 10.1016/j.cub.2007.07.047 17716899
8. Mellert DJ, Knapp JM, Manoli DS, Meissner GW, Baker BS. Midline crossing by gustatory receptor neuron axons is regulated by fruitless, doublesex and the Roundabout receptors. Development 137, 323–332. (2010). doi: 10.1242/dev.045047 20040498
9. Pan Y, and Bake BS. Genetic identification and separation of innate and experience-dependent courtship behaviors in Drosophila. Cell 156, 236–248. (2014). doi: 10.1016/j.cell.2013.11.041 24439379
10. Rezaval C, Pattnaik S, Pavlou HJ, Nojima T, Bruggemeier B, D’Souza LAD, et al. Activation of Latent Courtship Circuitry in the Brain of Drosophila Females Induces Male-like Behaviors. Curr Biol 26, 2508–2515. (2016). doi: 10.1016/j.cub.2016.07.021 27568592
11. Ryner LC, Goodwin SF, Castrillon DH, Anand A, Villella A, Baker BS, et al. (1996). Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene. Cell 87, 1079–1089. doi: 10.1016/s0092-8674(00)81802-4 8978612
12. Heinrichs V, Ryner LC, and Baker BS. (1998). Regulation of sex-specific selection of fruitless 5’ splice sites by transformer and transformer-2. Mol Cell Biol 18, 450–458. doi: 10.1128/mcb.18.1.450 9418892
13. Dornan AJ, Gailey DA, Goodwin SF. (2005). GAL4 enhancer trap targeting of the Drosophila sex determination gene fruitless. Genesis 42, 236–246. doi: 10.1002/gene.20143 16028231
14. 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, 404–426. doi: 10.1002/1097-4695(20000615)43:4<404::aid-neu8>3.0.co;2-d 10861565
15. Clough E, Jimenez E, Kim YA, Whitworth C, Neville MC, Hempel LU, et al.(2014). Sex- and tissue-specific functions of Drosophila doublesex transcription factor target genes. Dev Cell 31, 761–773. doi: 10.1016/j.devcel.2014.11.021 25535918
16. Fuller MT, Spradling AC. (2007). Male and female Drosophila germline stem cells: two versions of immortality. Science 316, 402–404. doi: 10.1126/science.1140861 17446390
17. Le Bras S, Van Doren M. (2006). Development of the male germline stem cell niche in Drosophila. Dev Biol 294, 92–103. doi: 10.1016/j.ydbio.2006.02.030 16566915
18. Sahut-Barnola I, Godt D, Laski FA, Couderc JL. (1995). Drosophila ovary morphogenesis: analysis of terminal filament formation and identification of a gene required for this process. Dev Biol 170, 127–135. doi: 10.1006/dbio.1995.1201 7601303
19. Godt D, Laski FA. (1995). Mechanisms of cell rearrangement and cell recruitment in Drosophila ovary morphogenesis and the requirement of bric a brac. Development 121, 173–187. 7867498
20. Song X, Zhu CH, Doan C, Xie T. (2002). Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science 296, 1855–1857. doi: 10.1126/science.1069871 12052957
21. Camara N, Whitworth C, Dove A, Van Doren M. (2019). Doublesex controls specification and maintenance of the gonad stem cell niches in Drosophila. Development. doi: 10.1242/dev.170001 31043421
22. Sheng XR, Posenau T, Gumulak-Smith JJ, Matunis E, Van Doren M, Wawersik M. (2009). Jak-STAT regulation of male germline stem cell establishment during Drosophila embryogenesis. Dev Biol 334, 335–344. doi: 10.1016/j.ydbio.2009.07.031 19643104
23. Demir E, Dickson BJ. (2005). fruitless splicing specifies male courtship behavior in Drosophila. Cell 121, 785–794. doi: 10.1016/j.cell.2005.04.027 15935764
24. Stockinger P, Kvitsiani D, Rotkopf S, Tirian L, and Dickson BJ. (2005). Neural circuitry that governs Drosophila male courtship behavior. Cell 121, 795–807. doi: 10.1016/j.cell.2005.04.026 15935765
25. Billeter JC, 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, 270–287. doi: 10.1002/cne.20177 15211467
26. Neville MC, Nojima T, Ashley E, Parker DJ, Walker J, Southall T,et al. (2014). Male-specific fruitless isoforms target neurodevelopmental genes to specify a sexually dimorphic nervous system. Curr Biol 24, 229–241. doi: 10.1016/j.cub.2013.11.035 24440396
27. 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, 2577–2582. 1907913
28. Kopp A, Duncan I, Godt D, and Carroll SB. (2000). Genetic control and evolution of sexually dimorphic characters in Drosophila. Nature 408, 553–559. doi: 10.1038/35046017 11117736
29. Luo SD, Baker BS. (2015). Constraints on the evolution of a doublesex target gene arising from doublesex’s pleiotropic deployment. Proc Natl Acad Sci U S A 112, E852–861. doi: 10.1073/pnas.1501192112 25675536
30. Wagamitsu S, Takase D, Aoki F, Suzuki MG. (2017). Identification of the Doublesex protein binding sites that activate expression of lozenge in the female genital disc in Drosophila melanogaster. Mech Dev 143, 26–31. doi: 10.1016/j.mod.2017.01.001 28087460
31. Lee T, Luo L. (1999). Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 22, 451–461. doi: 10.1016/s0896-6273(00)80701-1 10197526
32. Song HJ, Billeter JC, Reynaud E, Carlo T, Spana EP, Perrimon N, et al. (2002). The fruitless gene is required for the proper formation of axonal tracts in the embryonic central nervous system of Drosophila. Genetics 162, 1703–1724. 12524343
33. 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, 458–466. doi: 10.1038/nn.2515 20305646
34. Bolivar J, Pearson J, Lopez-Onieva L, Gonzalez-Reyes A. (2006). Genetic dissection of a stem cell niche: the case of the Drosophila ovary. Dev Dyn 235, 2969–2979. doi: 10.1002/dvdy.20967 17013875
35. Tran J, Brenner TJ, DiNardo S. (2000). Somatic control over the germline stem cell lineage during Drosophila spermatogenesis. Nature 407, 754–757. doi: 10.1038/35037613 11048723
36. Yi W, Zarkower D. (1999). Similarity of DNA binding and transcriptional regulation by Caenorhabditis elegans MAB-3 and Drosophila melanogaster DSX suggests conservation of sex determining mechanisms. Development 126, 873–881. 9927589
37. Luo SD, Shi GW, Baker BS. (2011). Direct targets of the D. melanogaster DSXF protein and the evolution of sexual development. Development 138, 2761–2771. doi: 10.1242/dev.065227 21652649
38. 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, 1532–1542. doi: 10.1016/j.cub.2016.04.067 27265393
39. Stine RR, Greenspan LJ, Ramachandran KV, Matunis EL. (2014). Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT signaling in the Drosophila testis. PLoS Genet 10, e1004713. doi: 10.1371/journal.pgen.1004713 25375180
40. 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, 378–390. doi: 10.1016/j.ydbio.2008.05.543 18599032
41. Shirangi TR, Dufour HD, Williams TM, Carroll SB. (2009). Rapid evolution of sex pheromone-producing enzyme expression in Drosophila. PLoS Biol 7, e1000168. doi: 10.1371/journal.pbio.1000168 19652700
42. Murphy MW, Sarver AL, Rice D, Hatzi K, Ye K, Melnick A, et al. (2010). Genome-wide analysis of DNA binding and transcriptional regulation by the mammalian Doublesex homolog DMRT1 in the juvenile testis. Proc Natl Acad Sci U S A 107, 13360–13365. doi: 10.1073/pnas.1006243107 20616082
43. Gailey DA, Billeter JC, Liu JH, Bauzon F, Allendorfer JB, Goodwin SF. (2006). Functional conservation of the fruitless male sex-determination gene across 250 Myr of insect evolution. Mol Biol Evol 23, 633–643. doi: 10.1093/molbev/msj070 16319090
44. Ustinova J, Mayer F. (2006). Alternative starts of transcription, several paralogues, and almost-fixed interspecific differences of the gene fruitless in a hemimetabolous insect. J Mol Evol 63, 788–800. doi: 10.1007/s00239-005-6230-2 17086452
45. Clynen E, Ciudad L, Belles X, Piulachs MD. (2011). Conservation of fruitless’ role as master regulator of male courtship behaviour from cockroaches to flies. Dev Genes Evol 221, 43–48. doi: 10.1007/s00427-011-0352-x 21340608
46. Boerjan B, Tobback J, Vandersmissen HP, Huybrechts R, Schoofs L. (2012). Fruitless RNAi knockdown in the desert locust, Schistocerca gregaria, influences male fertility. J Insect Physiol 58, 265–269. doi: 10.1016/j.jinsphys.2011.11.017 22138053
47. Davis T, Kurihara J, Yamamoto D. (2000). Genomic organisation and characterisation of the neural sex-determination gene fruitless (fru) in the Hawaiian species Drosophila heteroneura. Gene 246, 143–149. doi: 10.1016/s0378-1119(00)00064-0 10767535
48. Davis T, Kurihara J, Yoshino E, Yamamoto D. (2000). Genomic organisation of the neural sex determination gene fruitless (fru) in the Hawaiian species Drosophila silvestris and the conservation of the fru BTB protein-protein-binding domain throughout evolution. Hereditas 132, 67–78. doi: 10.1111/j.1601-5223.2000.00067.x 10857262
49. Gonczy P, Matunis E, DiNardo S. (1997). bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis. Development 124, 4361–4371. 9334284
Článek vyšel v časopise
PLOS Genetics
2021 Číslo 3
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Proč při poslechu některé muziky prostě musíme tančit?
- Chůze do schodů pomáhá prodloužit život a vyhnout se srdečním chorobám
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- „Jednohubky“ z klinického výzkumu – 2024/44
Nejčtenější v tomto čísle
- DNA polymerase theta suppresses mitotic crossing over
- IKAROS is required for the measured response of NOTCH target genes upon external NOTCH signaling
- activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis
- The etiology of Down syndrome: Maternal MCM9 polymorphisms increase risk of reduced recombination and nondisjunction of chromosome 21 during meiosis I within oocyte
