Finding clues to the riddle of sex determination in zebrafish
- 833 Downloads
- 8 Citations
Abstract
How sex is determined has been one of the most intriguing puzzles in biology since antiquity. Although a fundamental process in most metazoans, there seems to be myriad of ways in which sex can be determined – from genetic to environmental sex determination. This variation is limited mainly to upstream triggers with the core of sex determination pathway being conserved. Zebrafish has gained prominence as a vertebrate model system to study development and disease. However, very little is known about its primary sex determination mechanism. Here we review our current understanding of the sex determination in zebrafish. Zebrafish lack identifiable heteromorphic sex chromosomes and sex is determined by multiple genes, with some influence from the environment. Recently, chromosome 4 has been identified as sex chromosome along with few sex-linked loci on chromosomes 5 and 16. The identities of candidate sex-linked genes, however, have remained elusive. Sex in zebrafish is also influenced by the number of meiotic oocytes in the juvenile ovary, which appear to instruct retention of the ovarian fate. The mechanism and identity of this instructive signal remain unknown. We hypothesize that sex in zebrafish is a culmination of combinatorial effects of the genome, germ cells and the environment with inputs from epigenetic factors translating the biological meaning of this interaction.
Keywords
Epigenetic factors juvenile ovary PGC sex determination zebrafish ‘sex-biased‘ epigenomeNotes
Acknowledgements
We thank Centre of Excellence in Epigenetics, Department of Biotechnology, India, for funding. We thank K Ravinder for help and advice with the zebrafish experiments.
References
- Abozaid H, Wessels S and Hörstgen-Schwark G 2011 Effect of rearing temperatures during embryonic development on the phenotypic sex in zebrafish (Danio rerio). Sex. Dev. 5 259–265CrossRefPubMedGoogle Scholar
- Abozaid H, Wessels S and Hörstgen-Schwark G 2012 Elevated temperature applied during gonadal transformation leads to male bias in zebrafish (Danio rerio). Sex. Dev. 6 201–209CrossRefPubMedGoogle Scholar
- Amores A and Postlethwait JH 1999 Banded chromosomes and the zebrafish karyotype. Methods Cell Biol. 60 323–338CrossRefPubMedGoogle Scholar
- Anderson JL, Rodriguez Mari A, Braasch I, Amores A, Hohenlohe P, Batzel P and Postlethwait JH 2012 Multiple sex-associated regions and a putative sex chromosome in zebrafish revealed by RAD mapping and population genomics. PLoS One. 7 e40701CrossRefPubMedPubMedCentralGoogle Scholar
- Baroiller JF, D’Cotta H and Saillant E 2009 Environmental effects on fish sex determination and differentiation. Sex. Dev. 3 118–135CrossRefPubMedGoogle Scholar
- Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C and Schoenle EJ 2009 Ovaries and female phenotype in a girl with 46, XY karyotype and mutations in the CBX2 gene. Am. J. Hum. Genet. 84 658–663CrossRefPubMedPubMedCentralGoogle Scholar
- Bisoni L, Batlle-Morera L, Bird AP, Suzuki M and McQueen HA 2005 Female-specific hyperacetylation of histone H4 in the chicken Z chromosome. Chromosom. Res. 13 205–214CrossRefGoogle Scholar
- Bradley KM, Breyer JP, Melville DB, Broman KW, Knapik EW and Smith JR 2011 An SNP-based linkage map for zebrafish reveals sex determination loci. G3 (Bethesda) 1 3–9CrossRefGoogle Scholar
- Brennan J and Capel B 2004 One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat. Rev. Genet. 5 509–521CrossRefPubMedGoogle Scholar
- Chiang EF-L, Pai C-I, Wyatt M, Yan Y-L, Postlethwait J and Chung B 2001 Two sox9 genes on duplicated zebrafish chromosomes: expression of similar transcription activators in distinct sites. Dev. Biol. 231 149–163CrossRefPubMedGoogle Scholar
- Cutting A, Chue J and Smith CA 2013 Just how conserved is vertebrate sex determination? Dev. Dyn. Off. Publ. Am. Assoc. Anatomists 242 380–387Google Scholar
- Daga RR, Thode G and Amores A 1996 Chromosome complement, C-banding, Ag-NOR and replication banding in the zebrafish Danio rerio. Chromosom. Res. 4 29–32CrossRefGoogle Scholar
- Desjardins JK and Fernald RD 2009 Fish sex: why so diverse? Curr. Opin. Neurobiol. 19 648CrossRefPubMedPubMedCentralGoogle Scholar
- Devlin RH and Nagahama Y 2002 Sex determination and sex differentiation in fish: an overview of genetic, physiological, and environmental influences. Aquaculture 208 191–364CrossRefGoogle Scholar
- Dranow DB, Tucker RP and Draper BW 2013 Germ cells are required to maintain a stable sexual phenotype in adult zebrafish. Dev. Biol. 376 43–50CrossRefPubMedGoogle Scholar
- Gamble T and Zarkower D 2012 Sex determination. Curr. Biol. CB. 22 R257–R262CrossRefPubMedGoogle Scholar
- Gilchrist RB, Ritter LJ and Armstrong DT 2004 Oocyte-somatic cell interactions during follicle development in mammals. Anim. Reprod. Sci. 82–83 431–446CrossRefPubMedGoogle Scholar
- Gornung E, Gabrielli I, Cataudella S and Sola L 1997 CMA3-banding pattern and fluorescence in situ hybridization with 18S rRNA genes in zebrafish chromosomes. Chromosom. Res. 5 40–46CrossRefGoogle Scholar
- Grunwald DJ and Eisen JS 2002 Headwaters of the zebrafish — emergence of a new model vertebrate. Nat. Rev. Genet. 3 717–724CrossRefPubMedGoogle Scholar
- Guigon CJ and Magre S 2006 Contribution of germ cells to the differentiation and maturation of the ovary: insights from models of germ cell depletion. Biol. Reprod. 74 450–458CrossRefPubMedGoogle Scholar
- Guo Y, Cheng H, Huang X, Gao S, Yu H and Zhou R 2005 Gene structure, multiple alternative splicing, and expression in gonads of zebrafish Dmrt1. Biochem. Biophys. Res. Commun. 330 950–957CrossRefPubMedGoogle Scholar
- Hattori RS, Murai Y, Oura M, Masuda S, Majhi SK, Sakamoto T, Fernandino JI, Somoza GM, et al. 2012 A Y-linked anti-Müllerian hormone duplication takes over a critical role in sex determination. PNAS 109 2955–2959CrossRefPubMedPubMedCentralGoogle Scholar
- Herpin A and Schartl M 2008 Regulatory putsches create new ways of determining sexual development. EMBO Rep. 9 966–968CrossRefPubMedPubMedCentralGoogle Scholar
- Houwing S, Kamminga LM, Berezikov E, Cronembold D, Girard A, van den Elst H, Filippov DV, Blaser H, et al. 2007 A role for piwi and piRNAs in germ cell maintenance and transposon silencing in zebrafish. Cell. 129 69–82CrossRefPubMedGoogle Scholar
- Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, Collins JE, Humphray S, et al. 2013 The zebrafish reference genome sequence and its relationship to the human genome. Nature 496 498–503CrossRefPubMedPubMedCentralGoogle Scholar
- Jablonka E and Lamb MJ 1998 Epigenetic inheritance in evolution. J. Evol. Biol. 11 159–183CrossRefGoogle Scholar
- Jørgensen A, Morthorst JE, Andersen O, Rasmussen LJ and Bjerregaard P 2008 Expression profiles for six zebrafish genes during gonadal sex differentiation. Reprod. Biol. Endocrinol. 6 25CrossRefPubMedPubMedCentralGoogle Scholar
- Kashimada K and Koopman P 2010 Sry: the master switch in mammalian sex determination. Development. 137 3921–3930CrossRefPubMedGoogle Scholar
- Katoh-Fukui Y, Miyabayashi K, Komatsu T, Owaki A, Baba T, Shima Y, Kidokoro T, Kanai Y, et al. 2012 Cbx2, a polycomb group gene, is required for sry gene expression in mice. Endocrinology 153 913–924CrossRefPubMedGoogle Scholar
- Katoh-Fukui Y, Tsuchiya R, Shiroishi T, Nakahara Y, Hashimoto N, Noguchi K and Higashinakagawa T 1998 Male-to-female sex reversal in M33 mutant mice. Nature 393 688–692CrossRefPubMedGoogle Scholar
- Kopp A 2012 Dmrt genes in the development and evolution of sexual dimorphism. Trends Genet. 28 175–184CrossRefPubMedPubMedCentralGoogle Scholar
- Krøvel AV and Olsen LC 2004 Sexual dimorphic expression pattern of a splice variant of zebrafish vasa during gonadal development. Dev. Biol. 271 190–197CrossRefPubMedGoogle Scholar
- Kurokawa H, Saito D, Nakamura S, Katoh-Fukui Y, Ohta K, Baba T, Morohashi K and Tanaka M 2007 Germ cells are essential for sexual dimorphism in the medaka gonad. PNAS. 104 16958–16963CrossRefPubMedPubMedCentralGoogle Scholar
- Kuroki S, Matoba S, Akiyoshi M, Matsumura Y, Miyachi H, Mise N, Abe K, Ogura A, et al. 2013 Epigenetic regulation of mouse sex determination by the histone demethylase Jmjd1a. Science 341 1106–1109CrossRefPubMedGoogle Scholar
- Lawrence C, Ebersole JP, Kesseli RV (2008). Rapid growth and out-crossing promote female development in zebrafish (Danio rerio). Environ. Biol. Fishes. 81 239–246Google Scholar
- Lee ST, Lam TJ and Tan CH 2002 Increased 21-hydroxylase and shutdown of C(17,20) lyase activities in testicular tissues of the grouper (Epinephelus coioides) during 17alpha-methyltestosterone-induced sex inversion. Gen. Comp. Endocrinol. 126 298–309CrossRefPubMedGoogle Scholar
- Liew WC and Orbán L 2013 Zebrafish sex: a complicated affair. Briefings in functional genomics elt041Google Scholar
- Liew WC, Bartfai R, Lim Z, Sreenivasan R, Siegfried KR and Orban L 2012 Polygenic sex determination system in zebrafish. PLoS ONE 7 e34397CrossRefPubMedPubMedCentralGoogle Scholar
- Maack G and Segner H 2003 Morphological development of the gonads in zebrafish. J. Fish Biol. 62 895–906CrossRefGoogle Scholar
- Marı́n I and Baker BS 1998 The evolutionary dynamics of sex determination. Science 281 1990–1994CrossRefPubMedGoogle Scholar
- Matson CK and Zarkower D 2012 Sex and the singular DM domain: insights into sexual regulation, evolution and plasticity. Nat. Rev. Genet. 13 163–174PubMedPubMedCentralGoogle Scholar
- Matsuda M, Nagahama Y, Shinomiya A, Sato T, Matsuda C, Kobayashi T, Morrey CE, Shibata N, et al. 2002 DMY is a Y-specific DM-domain gene required for male development in the medaka fish. Nature 417 559–563CrossRefPubMedGoogle Scholar
- Matsumoto Y, Buemio A, Chu R, Vafaee M and Crews D 2013 Epigenetic control of gonadal aromatase (cyp19a1) in temperature-dependent sex determination of red-eared slider turtles. PLoS ONE 8 e63599CrossRefPubMedPubMedCentralGoogle Scholar
- McLaren A 1991 Development of the mammalian gonad: the fate of the supporting cell lineage. Bioessays 13 151–156CrossRefPubMedGoogle Scholar
- Meller VH, Wu KH, Roman G, Kuroda MI and Davis RL 1997 roX1 RNA paints the X chromosome of male Drosophila and is regulated by the dosage compensation system. Cell 88 445–457CrossRefPubMedGoogle Scholar
- Mishima Y, Giraldez AJ, Takeda Y, Fujiwara T, Sakamoto H, Schier AF and Inoue K 2006 Differential Regulation of Germline mRNAs in Soma and Germ Cells by Zebrafish miR-430. Curr. Biol. 16 2135–2142CrossRefPubMedPubMedCentralGoogle Scholar
- Morrish BC and Sinclair AH 2002 Vertebrate sex determination: many means to an end. Reproduction 124 447–457CrossRefPubMedGoogle Scholar
- Munger SC and Capel B 2012 Sex and the circuitry: progress toward a systems-level understanding of vertebrate sex determination. Wiley Interdiscip. Rev. Syst. Biol. Med. 4 401–412CrossRefPubMedGoogle Scholar
- Nakamura M, Kobayashi T, Chang X-T and Nagahama Y 1998 Gonadal sex differentiation in teleost fish. J. Exp. Zool. 281 362–372CrossRefGoogle Scholar
- Navarro-Martín L, Viñas J, Ribas L, Díaz N, Gutiérrez A, Di Croce L and Piferrer F 2011 DNA methylation of the gonadal aromatase (cyp19a) promoter is involved in temperature-dependent sex ratio shifts in the European sea bass. PLoS Genet. 7 e1002447CrossRefPubMedPubMedCentralGoogle Scholar
- Nelson JS 2006 Fishes of the world (John Wiley & Sons)Google Scholar
- Nüsslein-Volhard C and Dahm R 2002 Zebrafish: a practical approach (Oxford University Press, Incorporated)Google Scholar
- Ospina-Alvarez N and Piferrer F 2008 Temperature-dependent sex determination in fish revisited: prevalence, a single sex ratio response pattern, and possible effects of climate change. PLoS ONE 3 e2837CrossRefPubMedPubMedCentralGoogle Scholar
- Pannetier M, Fabre S, Batista F, Kocer A, Renault L, Jolivet G, Mandon-Pépin B, Cotinot C, et al. 2006 FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development. J. Mol. Endocrinol. 36 399–413CrossRefPubMedGoogle Scholar
- Parrott BB, Kohno S, Cloy-McCoy JA and Guillette LJ 2014 Differential incubation temperatures result in dimorphic DNA methylation patterning of the SOX9 and aromatase promoters in gonads of alligator (Alligator mississippiensis) embryos. Biol. Reprod. 90 2CrossRefPubMedGoogle Scholar
- Piferrer F 2013 Epigenetics of sex determination and gonadogenesis. Dev. Dyn. 242 360–370CrossRefPubMedGoogle Scholar
- Pradhan A, Khalaf H, Ochsner SA, Sreenivasan R, Koskinen J, Karlsson M, Karlsson J, McKenna NJ, et al. 2012 Activation of NF-κB protein prevents the transition from juvenile ovary to testis and promotes ovarian development in zebrafish. J. Biol. Chem. 287 37926–37938CrossRefPubMedPubMedCentralGoogle Scholar
- Rodríguez-Marí A, Cañestro C, BreMiller RA, Nguyen-Johnson A, Asakawa K, Kawakami K and Postlethwait JH 2010 Sex reversal in zebrafish fancl mutants is caused by Tp53-mediated germ cell apoptosis. PLoS Genet. 6 e1001034CrossRefPubMedPubMedCentralGoogle Scholar
- Rodríguez-Marí A, Yan Y-L, BreMiller RA, Wilson C, Cañestro C and Postlethwait JH 2005 Characterization and expression pattern of zebrafish anti-Müllerian hormone (amh) relative to sox9a, sox9b, and cyp19a1a, during gonad development. Gene Expr. Patterns 5 655–667CrossRefPubMedGoogle Scholar
- Roeszler KN, Itman C, Sinclair AH and Smith CA 2012 The long non-coding RNA, MHM, plays a role in chicken embryonic development, including gonadogenesis. Dev. Biol. 366 317–326CrossRefPubMedGoogle Scholar
- Ser JR, Roberts RB and Kocher TD 2010 Multiple interacting loci control sex determination in Lake Malawi Cichlid fishes. Evolution 64 486–501CrossRefPubMedGoogle Scholar
- Shang EHH, Yu RMK and Wu RSS 2006 Hypoxia affects sex differentiation and development, leading to a male-dominated population in zebrafish (Danio rerio). Environ. Sci. Technol. 40 3118–3122CrossRefPubMedGoogle Scholar
- Sharma KK, Sharrna OP and Tripathi NK 1998 Female heterogamety in Danio rerio (Cypriniformes: Cyprinidae). Proc. Natl. Acad. Sci. India Sect. B. 68 123–126Google Scholar
- Siegfried KR 2010 In search of determinants: gene expression during gonadal sex differentiation. J. Fish Biol. 76 1879–1902CrossRefPubMedGoogle Scholar
- Siegfried KR and Nüsslein-Volhard C 2008 Germ line control of female sex determination in zebrafish. Dev. Biol. 324 277–287CrossRefPubMedGoogle Scholar
- Slanchev K, Stebler J, de la Cueva-Méndez G and Raz E 2005 Development without germ cells: the role of the germ line in zebrafish sex differentiation. PNAS 102 4074–4079CrossRefPubMedPubMedCentralGoogle Scholar
- Sola L and Gornung E 2001 Classical and molecular cytogenetics of the zebrafish, Danio rerio (Cyprinidae, Cypriniformes): an overview. Genetica 111 397–412CrossRefPubMedGoogle Scholar
- Sreenivasan R, Cai M, Bartfai R, Wang X, Christoffels A and Orban L 2008 Transcriptomic analyses reveal novel genes with sexually dimorphic expression in the zebrafish gonad and brain. PLoS ONE 3 e1791CrossRefPubMedPubMedCentralGoogle Scholar
- Streisinger G, Walker C, Dower N, Knauber D and Singer F 1981 Production of clones of homozygous diploid zebra fish (Brachydanio rerio). Nature 291 293–296CrossRefPubMedGoogle Scholar
- Sun D, Zhang Y, Wang C, Hua X, Zhang XA and Yan J 2013 Sox9-related signaling controls zebrafish juvenile ovary–testis transformation. Cell Death Dis. 4 e930CrossRefPubMedPubMedCentralGoogle Scholar
- Teranishi M, Shimada Y, Hori T, Nakabayashi O, Kikuchi T, Macleod T, Pym R, Sheldon B, et al. 2001 Transcripts of the MHM region on the chicken Z chromosome accumulate as non-coding RNA in the nucleus of female cells adjacent to the DMRT1 locus. Chromosom. Res. 9 147–165CrossRefGoogle Scholar
- Trant JM, Gavasso S, Ackers J, Chung B-C and Place AR 2001 Developmental expression of cytochrome P450 aromatase genes (CYP19a and CYP19b) in zebrafish fry (Danio rerio). J. Exp. Zool. 290 475–483CrossRefPubMedGoogle Scholar
- Traut W and Winking H 2001 Meiotic chromosomes and stages of sex chromosome evolution in fish: zebrafish, platyfish and guppy. Chromosom. Res. 9 659–672CrossRefGoogle Scholar
- Uchida D, Yamashita M, Kitano T and Iguchi T 2004 An aromatase inhibitor or high water temperature induce oocyte apoptosis and depletion of P450 aromatase activity in the gonads of genetic female zebrafish during sex-reversal. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 137 11–20CrossRefPubMedGoogle Scholar
- Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier A-C, Klugmann C, et al. 2009 Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell 139 1130–1142CrossRefPubMedGoogle Scholar
- Volff JN and Schartl M 2001 Variability of genetic sex determination in poeciliid fishes. Genetica 111 101–110. Available from http://www.ncbi.nlm.nih.gov/pubmed/11841158
- Von Hofsten J and Olsson P-E 2005 Zebrafish sex determination and differentiation: involvement of FTZ-F1 genes. Reprod. Biol. Endocrinol. 3 63CrossRefGoogle Scholar
- Wallace BMN and Wallace H 2003 Synaptonemal complex karyotype of zebrafish. Heredity (Edinb) 90 136–140CrossRefGoogle Scholar
- Wang D-S, Kobayashi T, Zhou L-Y, Paul-Prasanth B, Ijiri S, Sakai F, Okubo K, Morohashi K, et al. 2007a Foxl2 up-regulates aromatase gene transcription in a female-specific manner by binding to the promoter as well as interacting with ad4 binding protein/steroidogenic factor 1. Mol. Endocrinol. 21 712–725CrossRefPubMedGoogle Scholar
- Wang XG, Bartfai R, Sleptsova-Freidrich I and Orban L 2007b The timing and extent of “juvenile ovary” phase are highly variable during zebrafish testis differentiation. J. Fish Biol. 70 33–44CrossRefGoogle Scholar
- Wilhelm D, Yang JX and Thomas P 2013 Mammalian sex determination and gonad development. Curr. Top. Dev. Biol. 106 89–121CrossRefPubMedGoogle Scholar
- Wilkins AS 1995 Moving up the hierarchy: a hypothesis on the evolution of a genetic sex determination pathway. Bioessays 17 71–77CrossRefPubMedGoogle Scholar
- Williams TM and Carroll SB 2009 Genetic and molecular insights into the development and evolution of sexual dimorphism. Nat. Rev. Genet. 10 797–804CrossRefPubMedGoogle Scholar
- Wilson CA, High SK, McCluskey BM, Amores A, Yan Y-L, Titus TA, Anderson JL, Batzel P, et al. 2014 Wild sex in zebrafish: loss of the natural sex determinant in domesticated strains. Genetics 198 1291–1308CrossRefPubMedPubMedCentralGoogle Scholar
- Wu JI, Lessard J and Crabtree GR 2009 Understanding the words of chromatin regulation. Cell 136 200–206CrossRefPubMedPubMedCentralGoogle Scholar