Ovarian development in mice requires the GATA4-FOG2 transcription complex

Manuylov, Nikolay L.; Smagulova, Fátima; Leach, Lyndsay L.; Tevosian, Sergei G.

doi:10.1242/dev.024653

Cited by 92 publications

(130 citation statements)

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“…Consistent with this model, RSPO1 protein is detected on the membrane of both cell types (Kocer et al 2008, Smith et al 2008, suggesting that CTNNB1 is directly activated in female germ cells to regulate their fate. Consistent with this hypothesis, germ cells of the XX embryos normally enter meiosis when Ctnnb1 is specifically ablated in somatic cells of the developing ovary (Sf1:cre; Ctnnb1 flox/flox mice; Manuylov et al 2008, Liu et al 2009). This suggests that WNT/b-catenin signaling in somatic ovarian cells does not affect germ cell fate.…”

Section: Rspo1 and Wnt4 Regulate Meiosis Entry Of Female Germ Cells mentioning

confidence: 67%

“…1). However, the conditional knockout of Ctnnb1 in somatic tissue of the ovary does not impair ovarian differentiation (Manuylov et al 2008, Liu et al 2009, suggesting that either the ablation of Ctnnb1 must occur within all ovarian cell types (somatic and germ cells) to promote sex reversal, or Rspo1 and Wnt4 activate pathways other than the WNT/CTNNB1 signaling pathway.…”

Section: R99mentioning

confidence: 99%

“…In the embryonic mouse ovary, Foxl2 expression is partly dependent on RSPO1 and CTNNB1 (Manuylov et al 2008, Auguste et al 2011, whereas it is normally expressed in the Wnt4 K/K ovary (Manuylov et al 2008), suggesting that Foxl2 is expressed in two different somatic cell populations. Moreover, simultaneous deletion of Foxl2 K/K and Wnt4 K/K , as well as Foxl2…”

Section: Rspo1 Wnt4 and Foxl2 Relationship In Ovarian Developmentmentioning

confidence: 99%

“…It is likely that sex reversal is promoted by a signal derived from abnormally differentiated germ cells in Rspo1 and Wnt4 mutants, whereas this signal is not produced in Sf1cre; Ctnnb1 flox/flox embryos. Thus, the differentiation of germ cells is unaffected before they undergo apoptosis in Sf1cre; Ctnnb1 flox/flox gonads unlike in Rspo1 K/K and Wnt4 K/K gonads (Manuylov et al 2008, Liu et al 2009. However, it is not clear as to how germ cells promote sex reversal to occur in Rspo1 and Wnt4 knockout XX gonads (Maatouk et al 2013).…”

Section: Remaining Questions and Prospectsmentioning

confidence: 99%

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R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation

Chassot¹,

Gillot²,

Chaboissier³

2014

Reproduction

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Sex differentiation is a unique developmental process. Starting from a bipotential gonad, it gives rise to the ovary and the testis, two highly specialized organs that differ morphologically and physiologically despite sharing common reproductive and endocrine functions. This highlights the specific plasticity of the gonadal precursors and the existence of complex antagonistic genetic regulation. Mammalian sex determination is controlled by paternal transmission of the Y-linked gene, sex-determining region Y (SRY). Using mouse models, it has been shown that the main role of Sry is to activate the expression of the transcription factor Sox9; either one of these two genes is necessary and sufficient to allow testicular development through Sertoli cell differentiation. Thus, defects in SRY/Sry and/or SOX9/Sox9 expression result in male-to-female sex reversal of XY individuals. Molecular mechanisms governing ovarian differentiation remained unknown for a long time, until the discovery of the roles of R-spondin1 (RSPO1) and WNT4. In XX individuals, activation of the b-catenin signaling pathway by the secreted proteins RSPO1 and WNT4 is required to allow granulosa cell differentiation and, in turn, ovarian differentiation. Thus, mutations in RSPO1 result in female-to-male sex reversal of XX patients, and mouse models have allowed the identification of genetic cascades activated by RSPO1 and WNT4 to regulate ovarian development. In this review, we will discuss the respective roles of RSPO1, WNT4, and the b-catenin signaling pathway during ovarian differentiation in mice.Reproduction (2014) 148 R97-R110

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Section: Rspo1 and Wnt4 Regulate Meiosis Entry Of Female Germ Cells mentioning

confidence: 67%

Section: R99mentioning

confidence: 99%

Section: Rspo1 Wnt4 and Foxl2 Relationship In Ovarian Developmentmentioning

confidence: 99%

Section: Remaining Questions and Prospectsmentioning

confidence: 99%

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R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation

Chassot¹,

Gillot²,

Chaboissier³

2014

Reproduction

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“…This situation prompted the development of genetically-modified mouse models that circumvent early embryonic lethality and now provide clear evidence for a crucial and complex GATA4 role in the gonads. These partial and/or conditional Gata4 loss-offunction models indicate that GATA4 is first required for normal gonad development in both sexes and then later for the proper function of the mature testis and the ovary [8,9,10,11,12].…”

Section: Introductionmentioning

confidence: 99%

An E-Box Element in the Proximal GATA4 Promoter Is Required for Gata4 Expression In Vivo.

Boulende¹,

Béland²,

Bouchard³

et al. 2010

Biology of Reproduction

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GATA4 is an essential transcription factor required for the development and function of multiple tissues, including a major role in gonadogenesis. Despite its crucial role, the molecular mechanisms that regulate Gata4 expression in vivo remain poorly understood. We recently found that the Gata4 gene is expressed as multiple transcripts with distinct 59 origins. These co-expressed alternative transcripts are generated by different non-coding first exons with transcripts E1a and E1b being the most prominent. Moreover, we previously showed that an Ebox element, located in Gata4 59 flanking sequences upstream of exon 1a, is important for the promoter activity of these sequences in cell lines. To confirm the importance of this element in vivo, we generated and characterized Gata4 Ebox knockout mice. Quantitative PCR analyses realized on gonads, heart and liver at three developmental stages (embryonic, pre-pubertal and adult) revealed that the Ebox mutation leads to a robust and specific decrease (up to 89%) of Gata4 E1a transcript expression in all tissues and stages examined. However, a detailed characterization of the gonads revealed normal morphology and GATA4 protein levels in these mutants. Our qPCR data further indicate that this outcome is most likely due to the presence of Gata4 E1b mRNA, whose expression levels were not decreased by the Ebox mutation. In conclusion, our work clearly confirms the importance of the proximal Ebox element and suggests that adequate GATA4 protein expression is likely protected by a compensation mechanism between Gata4 E1a and E1b transcripts operating at the translational level.

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Sexual Differentiation, Gonadal Development, and Development of the External Genitalia

Perrett¹

2018

Clinical Reproductive Science

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Ovarian development in mice requires the GATA4-FOG2 transcription complex

Cited by 92 publications

References 84 publications

R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation

R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation

An E-Box Element in the Proximal GATA4 Promoter Is Required for Gata4 Expression In Vivo.

Sexual Differentiation, Gonadal Development, and Development of the External Genitalia

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