Loss of dmrt1 restores female fates in the absence of cyp19a1a but not rbpms2a/b

Romano, Shannon N.; Kaufman, Odelya H.; Marlow, Florence

doi:10.1242/dev.190942

Cited by 25 publications

(36 citation statements)

References 83 publications

(121 reference statements)

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“…However, AI treatment failed to rescue the male-to-female sex reversal in dmrt1 Δ5/Δ5 XY tilapia. Consistently, in zebrafish, mutation of cyp19a1a failed to rescue the male-tofemale sex reversal in the early stages of dmrt1 mutants (Wu et al, 2020;Romano et al, 2020). These results further confirmed that Dmrt1 is essential for male germ cell fate decision.…”

Section: Discussionsupporting

confidence: 69%

“…As discussed above, the presence of Dmrt1 is the prerequisite for occurrence of spermatogenesis in a female environment after loss of foxl3. A recent study in zebrafish showed that in the context of dmrt1 loss, aromatase/Cyp19a1a is dispensable for early oocyte development (Wu et al, 2020;Romano et al, 2020). Different from the tilapia dmrt1 Δ5/Δ5 XY and foxl3 Δ7/Δ7 XX single mutants, in which the sex of germ cells was not rescued by AI and estrogen treatment, respectively, the germline sexual fate was dependent on the somatic cell environment in the dmrt1 and foxl3 double mutants.…”

Section: Discussionmentioning

confidence: 94%

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Germline sexual fate is determined by the antagonistic action of dmrt1 and foxl3/foxl2 in tilapia

Dai

Xu-bin

et al. 2021

Development

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Germline sexual fate has long been believed to be determined by the somatic environment, but this idea is challenged by recent studies of foxl3 mutants in medaka. Here we demonstrate that the sexual fate of tilapia germline is determined by the antagonistic interaction of dmrt1 and foxl3, which are transcriptionally repressed in male and female germ cells, respectively. Loss of dmrt1 rescued the germ cell sex reversal in foxl3Δ7/Δ7 XX fish, and loss of foxl3 partially rescued germ cell sex reversal but not somatic cell fate in dmrt1Δ5/Δ5 XY fish. Interestingly, germ cells lost sexual plasticity in dmrt1Δ5/Δ5 XY and foxl3Δ7/Δ7 XX single mutants, as aromatase inhibitor and estrogen treatment failed to rescue the respective phenotypes. However, recovery of germ cell sexual plasticity was observed in dmrt1/foxl3 double mutants. Importantly, mutation of somatic cell specific foxl2 resulted in testicular development in foxl3Δ7/Δ7 or dmrt1Δ5/Δ5 mutants. Our findings demonstrate that sexual plasticity of germ cells relies on the presence of both dmrt1 and foxl3. The existence of dmrt1 and foxl3 allows environmental factors to influence the sex fate decision in vertebrates.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 94%

Germline sexual fate is determined by the antagonistic action of dmrt1 and foxl3/foxl2 in tilapia

Dai

Xu-bin

et al. 2021

Development

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“…DMRT1 protein levels appeared to be higher in the dorsal aspect than in the ventral aspect of the gonad: in partially sexreversed gonads, the ventral medulla contained FOXL2 and aromatase +ve cells expressing low levels of DMRT1protein, while the dorsal medulla contained SOX9 +ve cells expressing high levels of DMRT1 protein. These findings are consistent with reports on other nonmammalian vertebrates, where exposure to estrogen results in male-to-female sex-reversal and inhibiting estriogen leads to female-to-male sex-reversal (29)(30)(31)(32)(33)(34)(35). In many instances, manipulating estrogen levels affects expression of DMRT1.…”

Section: Discussionsupporting

confidence: 91%

Estrogen suppresses DMRT1 expression during ovarian development in the chicken

Zhao

Liu

Nandi

et al. 2022

Preprint

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Primary sex determination is the choice between two different developmental fates, a testis or an ovary. This selection is thought to require the action of a master regulator gene that triggers expression of a gene cascade in the bipotential gonad precursor in one sex. The selection of a particular developmental pathway is also thought to suppress the alternative developmental pathway.In birds, where the male is the homogametic sex (ZZ) and females the heterogametic sex (ZW), the Z-linked transcription factor DMRT1 is considered the master regulator and has been shown to be essential for testis development, and to also inhibit the ovarian pathway. Here, we characterise in detail, DMRT1 transcription and protein levels during gonadal development in the chick. Our analysis suggests that DMRT1 protein levels are equivalent in male and female gonads during the bipotential phase of development, and that DMRT1 protein levels are reduced in the developing ovary during the differentiation phase. The reduction in DMRT1 protein levels in the somatic cells of the female medulla, coincides with the induction of aromatase expression and the initiation of estrogen synthesis. Analysis of sex-reversed gonads and mixed-sex chimeric gonads, suggests that the reduction in DMRT1 protein is due to inhibition of DMRT1 expression by estrogen.Our data suggests that estrogen signalling is involved in primary sex determination by regulation of DMRT1 protein expression.

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“…All-male Yes Unknown (Romano et al, 2020) rbm46 All-male Yes Male bias and infertility remained (Dai et al, 2021) wnt4a…”

Section: Fundingmentioning

confidence: 99%

Bloom syndrome helicase contributes to germ line development and longevity in zebrafish

Annus

Müller

Jezsó

et al. 2021

Preprint

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RecQ helicases - also known as the ‘guardians of the genome’ - play crucial roles in genome integrity maintenance through their involvement in various DNA metabolic pathways. Aside from being conserved from bacteria to vertebrates, their importance is also reflected in the fact that in humans impaired function of multiple RecQ helicase orthologs are known to cause severe sets of problems, including Bloom, Werner or Rothmund-Thomson syndromes. Our aim was to create and characterize a zebrafish (Danio rerio) disease model for Bloom syndrome, a recessive autosomal disorder. In humans, this syndrome is characterized by short stature, skin rashes, reduced fertility, increased risk of carcinogenesis and shortened life expectancy brought on by genomic instability. We show that zebrafish blm mutants recapitulate major hallmarks of the human disease, such as shortened lifespan and reduced fertility. Moreover, similarly to other factors involved in DNA repair, some functions of zebrafish Blm bear additional importance in germ line development, and consequently in sex differentiation. Unlike fanc genes and rad51, however, blm appears to effect its function independent of tp53. Therefore, our model will be a valuable tool for further understanding the developmental and molecular attributes of this rare disease, along with providing novel insights into the role of genome maintenance proteins in somatic DNA repair and fertility.

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Loss of dmrt1 restores female fates in the absence of cyp19a1a but not rbpms2a/b

Cited by 25 publications

References 83 publications

Germline sexual fate is determined by the antagonistic action of dmrt1 and foxl3/foxl2 in tilapia

Germline sexual fate is determined by the antagonistic action of dmrt1 and foxl3/foxl2 in tilapia

Estrogen suppresses DMRT1 expression during ovarian development in the chicken

Bloom syndrome helicase contributes to germ line development and longevity in zebrafish

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