SOX9 Regulates Prostaglandin D Synthase Gene Transcription in Vivo to Ensure Testis Development

Wilhelm, Dagmar; Hiramatsu, Ryuji; Mizusaki, Hirofumi; Widjaja, Laura; Combes, Alexander N.; Kanai‐Azuma, Masami; Koopman, Peter

doi:10.1074/jbc.m609578200

Cited by 212 publications

(172 citation statements)

References 50 publications

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“…In male sex-determination pathways, sex-determination genes, including Sry, Dmrt1, and Sox9, induce testis differentiation. 10,11) In bipotential, undifferentiated gonads, Sox9 induces testis differentiation gene expression and promotes Sertoli cell differentiation. 12) There are two independent sexdetermination pathways in female development: the Foxl2 transcription factor pathway and the Rspo1/β-catenin pathway.…”

Section: De Novo Transcriptome Sequencing To Identify the Sex-determimentioning

confidence: 99%

De novotranscriptome sequencing to identify the sex-determination genes inHyriopsis schlegelii

Shi

Hong

Sheng

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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Section: De Novo Transcriptome Sequencing To Identify the Sex-determimentioning

confidence: 99%

De novotranscriptome sequencing to identify the sex-determination genes inHyriopsis schlegelii

Shi

Hong

Sheng

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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“…At this developmental stage the expression of the Fibroblast growth factor family member Fgf9 is required for somatic sex determination and germ cell survival in males (DiNapoli et al, 2006). Similarly a member of the prostaglandin family prostaglandin D2 is male specifically expressed in somatic and germ cells and plays a role in Sertoli cell recruitment and differentiation (Adams and McLaren, 2002;Wilhelm et al, 2005;Wilhelm et al, 2007a). The potential role of these signalling molecules to promote male development of the germ cell lineage is as yet unknown.…”

Section: Germ Cell Sex Determinationmentioning

confidence: 99%

Foetal germ cells: striking the balance between pluripotency and differentiation

Western¹

2009

Int. J. Dev. Biol.

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“…SOX9 may be able to take over SRY function when SRY is absent or no longer expressed. Unlike SRY, gonadal target genes of SOX9 have been identified in vitro and in vivo, including Amh, Pgds and Vanin1 , Wilhelm et al, 2007, Wilson et al, 2005.…”

Section: Introductionmentioning

confidence: 99%

Human SRY inhibits β-catenin-mediated transcription

Bernard

Sim

Knower

et al. 2008

The International Journal of Biochemistry & Cell Biology

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In most mammals, sex is determined by the presence or absence of the SRY gene. SRY encodes a DNA binding HMG-box transcription factor which, during embryogenesis, is the initial trigger of testis differentiation from the bipotential gonad, yet its precise mode of function remains unclear. In ovarian development, R-spondin1 and Wnt4 act through the Wnt/β-catenin signaling pathway to regulate TCF-dependent expression of unknown target genes and repress testis development. Conversely, SRY may be necessary to prevent the development of ovaries by inhibiting the action of ovarian-determining genes. We hypothesize that SRY prevents Wnt/β-catenin signaling, thereby inhibiting ovarian development. In HEK293T cells, SRY repressed β-catenin-mediated TCFdependent gene activation in the presence of a specific GSK3β inhibitor or an activated β-catenin mutant, suggesting that SRY inhibits Wnt signaling at the level of β-catenin. Three SRY mutant proteins with nuclear localization defects, encoded by XY male-to-female patients, failed to inhibit β-catenin; surprisingly four SRY sex reversed mutants with defective DNA binding activity showed near wild-type SRY inhibitory activity. Moreover the potent transactivator SRY-VP16 fusion protein also showed wild-type SRY inhibitory activity. Thus SRY inhibition of β-catenin involves neither DNA binding nor transactivation functions of SRY. β-catenin and SRY interact in-vitro and SRY expression triggered β-catenin localization into specific nuclear bodies in NT2/D1 and Hela cells. We conclude that SRY inhibits β-catenin-mediated Wnt signaling by a novel nuclear function of SRY that could be important in sex determination.

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SOX9 Regulates Prostaglandin D Synthase Gene Transcription in Vivo to Ensure Testis Development

Cited by 212 publications

References 50 publications

De novotranscriptome sequencing to identify the sex-determination genes inHyriopsis schlegelii

De novotranscriptome sequencing to identify the sex-determination genes inHyriopsis schlegelii

Foetal germ cells: striking the balance between pluripotency and differentiation

Human SRY inhibits β-catenin-mediated transcription

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