&lt;i&gt;Xenopus&lt;/i&gt; W-Linked DM-W Induces &lt;i&gt;Foxl2&lt;/i&gt; and &lt;i&gt;Cyp19&lt;/i&gt; Expression during Ovary Formation

Okada, Ema; Yoshimoto, Shin; Ikeda, Nozomi; Kanda, Hiromi; Tamura, Kei; Shiba, Tadayoshi; Takamatsu, Nobuhiko; Ito, Michihiko

doi:10.1159/000200080

Cited by 37 publications

(23 citation statements)

References 26 publications

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“…5A), estrogen probably acts downstream of DM-W in the normal ovary-formation cascade. In fact, we recently showed that ectopic DM-W upregulates the expression of Cyp19, which encodes the estrogensynthesizing enzyme P450 aromatase, and of Foxl2 in ZZ gonads (Okada et al, 2009). DMRT1 may directly decrease Foxl2 and/or Cyp19 expression as a repressor, or indirectly as an activator of another factor, in ZW gonads; in either case, DM-W may function to antagonize this activity.…”

Section: Research Article Dmrt1/dm-w In Xenopus Sex Determinationmentioning

confidence: 99%

“…In X. laevis, we showed that DM-W is expressed transiently during sex determination, and that some transgenic ZZ tadpoles carrying DM-W expression vectors have primary ovarian structures (Yoshimoto et al, 2008). Moreover, exogenous DM-W in ZZ gonads upregulates the expression of at least two ZW gonad-specific genes, Foxl2 and the aromatase gene Cyp19, during and after sex determination (Okada et al, 2009). These results suggest that the W-linked DM-W is a candidate for a sex (ovary)-determining gene for the ZZ/ZW-type system in X. laevis.…”

Section: Introductionmentioning

confidence: 97%

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Opposite roles ofDMRT1and its W-linked paralogue,DM-W, in sexual dimorphism ofXenopus laevis: implications of a ZZ/ZW-type sex-determining system

et al. 2010

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SUMMARYA Y-linked gene, DMY/dmrt1bY, in teleost fish medka and a Z-linked gene, DMRT1, in chicken are both required for male sex determination. We recently isolated a W-linked gene, DM-W, as a paralogue of DMRT1 in Xenopus laevis, which has a ZZ/ZW-type sex-determining system. The DNA-binding domain of DM-W shows high sequence identity with that of DMRT1, but DM-W has no significant sequence similarity with the transactivation domain of DMRT1. Here, we first show colocalization of DM-W and DMRT1 in the somatic cells surrounding primordial germ cells in ZW gonad during sex determination. We next examined characteristics of DM-W and DMRT1 as a transcription factor in vitro. DM-W and DMRT1 shared a DNA-binding sequence. Importantly, DM-W dose-dependently antagonized the transcriptional activity of DMRT1 on a DMRT1-driven luciferase reporter system in 293 cells. We also examined roles of DM-W or DMRT1 in gonadal formation. Some transgenic ZW tadpoles bearing a DM-W knockdown vector had gonads with a testicular structure, and two developed into frogs with testicular gonads. Ectopic DMRT1 induced primary testicular development in some ZW individuals. These observations indicated that DM-W and DMRT1 could have opposite functions in the sex determination. Our findings support a novel model for a ZZ/ZW-type system in which DM-W directs female sex as a sex-determining gene, by antagonizing DMRT1. Additionally, they suggest that DM-W diverged from DMRT1 as a dominant-negative type gene, i.e. as a 'neofunctionalization' gene for the ZZ/ZW-type system. Finally, we discuss a conserved role of DMRT1 in testis formation during vertebrate evolution.

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Section: Research Article Dmrt1/dm-w In Xenopus Sex Determinationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Opposite roles ofDMRT1and its W-linked paralogue,DM-W, in sexual dimorphism ofXenopus laevis: implications of a ZZ/ZW-type sex-determining system

et al. 2010

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“…In this frog species, both genetic and phenotypic sex can be determined [Miura et al, 1998], and gene expression levels in differentiating GMCs can be studied separately in genetic males and females. GMC gene expression patterns during sex differentiation have only been studied in a few other frog species, including Xenopus laevis [Semba et al, 1996;Koyano et al, 1997;Takase et al, 1999;Nakajima et al, 2000;Kawano et al, 2001;Lutz et al, 2001;Akatsuka et al, 2005;Osawa et al, 2005;Yoshimoto et al, 2006Yoshimoto et al, , 2008Urbatzka et al, 2007Urbatzka et al, , 2010Okada et al, 2009], Silurana ( Xenopus) tropicalis [El Jamil et al, 2008a;Duarte-Guterman and Trudeau, 2011], Engystomops ( Physalaemus) pustulosus [Duarte-Guterman et al, 2012] or Lithobates catesbeianus (formerly Rana catesbeiana ) [Mayer et al, 2002]. In these reports, 3 genes have consistently exhibited sexually dimorphic expression patterns in gonads of adult frogs and differentiating tadpoles.…”

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confidence: 99%

Sexing Frogs by Real-Time PCR: Using Aromatase (cyp19) as an Early Ovarian Differentiation Marker

Navarro‐Martín

Velasco-Santamaría²,

Duarte‐Guterman³

et al. 2012

Sex Dev

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Most anurans have no identified sex-markers; therefore, alternative methods for identification of early changes in sex ratios are required. In this study, Lithobates sylvaticus and Silurana tropicalis tadpoles were sampled at different developmental stages covering the entire process of sex differentiation. Three candidate genes known to be involved in sex differentiation in other vertebrate species were selected to develop a method to identify phenotypic sex in frogs: cytochrome p450 aromatase (cyp19), forkhead box L2 (foxl2) and the cytochrome 17-alpha-hydroxylase/17,20 lyase (cyp17). Cloning of these genes revealed nucleotide identity values ranging between 75–97% when compared to other amphibian species. Gene expression of cyp17,cyp19 and foxl2 in L. sylvaticus adult gonads and gonad-mesonephros complex (GMC) of tadpoles was analyzed by real-time RT-PCR. Results showed clear sexually dimorphic patterns in the expression of the 3 genes. Our analysis reveals that GMC gene expression levels of cyp19 alone can be used as a robust predictor of phenotypic sex in L. sylvaticus tadpoles. In addition, we validated this method measuring cyp19 mRNA levels in S. tropicalis GMCs. We propose measuring cyp19 as a tool to study the effects of chemical contaminants (including endocrine disrupting compounds) on amphibian gonadal development and sex ratios in the future.

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“…Nevertheless, evidence is accumulating to suggest that FOXL2 is an important ovarian differentiating gene. Indeed, its ovarian-specific expression is conserved in all vertebrate species studied until now [Loffler et al, 2003;Baron et al, 2004;Govoroun et al, 2004;Wang et al, 2004;Nakamoto et al, 2006;Liu et al, 2007;Rhen et al, 2007;Wotton et al, 2007;Alam et al, 2008;Ijiri et al, 2008;Oshima et al, 2008;Siegfried and Nusslein-Volhard, 2008;Nakamoto et al, 2009;Okada et al, 2009;Shi et al, 2009;Amberg et al, 2010;Moore et al, 2010;Shoemaker-Daly et al, 2010;Wu et al, 2010], and in an invertebrate species such as the pacific oyster [Naimi et al, 2009]. In addition to the function of Foxl2 in development, Foxl2 is also required for ovarian homeostasis.…”

mentioning

confidence: 99%

Loss of R-Spondin1 and Foxl2 Amplifies Female-to-Male Sex Reversal in XX Mice

Auguste

Chassot

Gregoire

et al. 2011

Sex Dev

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In vertebrates, 2 main genetic pathways have been shown to regulate ovarian development. Indeed, a loss of function mutations in Rspo1 and Foxl2 promote partial female-to-male sex reversal. In mice, it has been shown that the secreted protein RSPO1 is involved in ovarian differentiation and the transcription factor FOXL2 is required for follicular formation. Here, we analysed the potential interactions between these 2 genetic pathways and have shown that while Rspo1 expression seems to be independent of Foxl2 up-regulation, Foxl2 expression partly depends of Rspo1 signalisation. This suggests that different Foxl2-positive somatic cell lineages exist within the ovaries. In addition, a combination of both mutated genes in XX Foxl2^–/–/Rspo1^–/– gonads promotes sex reversal, detectable at earlier stages than in XX Rspo1^–/– mutants. Ectopic development of the steroidogenic lineage is more pronounced in XX Foxl2^–/–/Rspo1^–/– gonads than in XX Rspo1^–/– embryos, suggesting that Foxl2 is involved in preventing ectopic steroidogenesis in foetal ovaries.

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<i>Xenopus</i> W-Linked DM-W Induces <i>Foxl2</i> and <i>Cyp19</i> Expression during Ovary Formation

Cited by 37 publications

References 26 publications

Opposite roles ofDMRT1and its W-linked paralogue,DM-W, in sexual dimorphism ofXenopus laevis: implications of a ZZ/ZW-type sex-determining system

Opposite roles ofDMRT1and its W-linked paralogue,DM-W, in sexual dimorphism ofXenopus laevis: implications of a ZZ/ZW-type sex-determining system

Sexing Frogs by Real-Time PCR: Using Aromatase <b><i>(cyp19) </i></b>as an Early Ovarian Differentiation Marker

Loss of <i>R-Spondin1</i> and <i>Foxl2</i> Amplifies Female-to-Male Sex Reversal in XX Mice

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