Cell fate commitment during mammalian sex determination

Lin, Yi-Tzu; Capel, Blanche

doi:10.1016/j.gde.2015.03.003

Cited by 99 publications

(83 citation statements)

References 105 publications

(116 reference statements)

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“…Combined, these data indicate that FGF9, activin and TGFβ act together to promote Sox9 transcription and some testicular characteristics in intact cultured XX gonads and limited expression of SOX9 and AMH protein. This conclusion is consistent with previous observations that activin/ TGFβ signalling is required for testis cord formation and Sertoli cell proliferation in E11.5-E12.5 XY gonads ) and the established role for FGF9 in testis development (Lin & Capel 2015). Although we observed increased Sox9, Cyp26b1 and Inhba transcription and some SOX9+ and AMH+ cells in FAT-treated XX gonads, Dhh was not upregulated, indicating that Sertoli cell development was restricted in this system.…”

Section: Growth Factors Fgf9 Activin and Tgfβ Promote Testicular Chasupporting

confidence: 93%

“…In mice, testis development is initiated by expression of the Y-chromosome-linked testis-determining gene Sry (sex-determining region of chromosome Y). SRY promotes pre-Sertoli cell proliferation and expression of the dominant male sex-determining transcription factor Sox9 (Sry-box containing gene 9), leading to commitment of bipotential pre-supporting cells to Sertoli cell development and testis differentiation (Lin & Capel 2015). As Sertoli cells proliferate, they organise into laminin-delineated testis cords that surround germ cells, thereby defining the interstitial space where steroidogenic Leydig cells differentiate (Lin & Capel 2015).…”

Section: Introductionmentioning

confidence: 99%

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FGF9, activin and TGFβ promote testicular characteristics in an XX gonad organ culture model

et al. 2016

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Testis development is dependent on the key sex-determining factors SRY and SOX9, which activate the essential ligand FGF9. Although FGF9 plays a central role in testis development, it is unable to induce testis formation on its own. However, other growth factors, including activins and TGFβs, also present testis during testis formation. In this study, we investigated the potential of FGF9 combined with activin and TGFβ to induce testis development in cultured XX gonads. Our data demonstrated differing individual and combined abilities of FGF9, activin and TGFβ to promote supporting cell proliferation, Sertoli cell development and male germ line differentiation in cultured XX gonads. FGF9 promoted proliferation of supporting cells in XX foetal gonads at rates similar to those observed in vivo during testis cord formation in XY gonads but was insufficient to initiate testis development. However, when FGF9, activin and TGFβ were combined, aspects of testicular development were induced, including the expression of Sox9, morphological reorganisation of the gonad and deposition of laminin around germ cells. Enhancing β-catenin activity diminished the testis-promoting activities of the combined growth factors. The male promoting activity of FGF9 and the combined growth factors directly or indirectly extended to the germ line, in which a mixed phenotype was observed. FGF9 and the combined growth factors promoted male germ line development, including mitotic arrest, but expression of pluripotency genes was maintained, rather than being repressed. Together, our data provide evidence that combined signalling by FGF9, activin and TGFβ can induce testicular characteristics in XX gonads.Reproduction (2016) 152 529-543

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Section: Growth Factors Fgf9 Activin and Tgfβ Promote Testicular Chasupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

FGF9, activin and TGFβ promote testicular characteristics in an XX gonad organ culture model

et al. 2016

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“…Sox9 is a direct effector of the mammalian somatic sex determination gene, Sry . Sry is a mammalian‐specific gene, while Sox9 is conserved among vertebrates 50. However, our recent analysis indicated that sox9b − an orthologue of the mammalian Sox9 expressed in the supporting cells − is not directly involved in testicular differentiation.…”

Section: Neofunctionalization Of Other Genes With Loss Of Germline Stmentioning

confidence: 96%

Germline stem cells are critical for sexual fate decision of germ cells

Tanaka

2016

BioEssays

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Egg or sperm? The mechanism of sexual fate decision in germ cells has been a long‐standing issue in biology. A recent analysis identified foxl3 as a gene that determines the sexual fate decision of germ cells in the teleost fish, medaka. foxl3/Foxl3 acts in female germline stem cells to repress commitment into male fate (spermatogenesis), indicating that the presence of mitotic germ cells in the female is critical for continuous sexual fate decision of germ cells in medaka gonads. Interestingly, foxl3 is found in most vertebrate genomes except for mammals. This provides the interesting possibility that the sexual fate of germ cells in mammals is determined in a different way compared to foxl3‐possessing vertebrates. Considering the fact that germline stem cells are the cells where foxl3 begins to express and sexual fate decision initiates and mammalian ovary does not have typical germline stem cells, the mechanism in mammals may have been co‐evolved with germline stem cell loss in mammalian ovary.

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“…Gonadal differentiation into a testis or an ovary requires a delicate dosage balance in the timing and levels of expression of several genes [Lin and Capel, 2015]. In most mammalian embryos, the transient expression of SRY , which maps to the Y chromosome, triggers a cascade of gene interactions ultimately leading to the formation of a testis from the indifferent gonadal ridge [Larney et al, 2014].…”

Section: Introductionmentioning

confidence: 99%

Disorders of Sex Development with Testicular Differentiation in SRY-Negative 46,XX Individuals: Clinical and Genetic Aspects

Grinspon

Rey

2016

Sex Dev

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Virilisation of the XX foetus is the result of androgen excess, resulting most frequently from congenital adrenal hyperplasia in individuals with typical ovarian differentiation. In rare cases, 46,XX gonads may differentiate into testes, a condition known as 46,XX testicular disorders of sex development (DSD), or give rise to the coexistence of ovarian and testicular tissue, a condition known as 46,XX ovotesticular DSD. Testicular tissue differentiation may be due to the translocation of SRY to the X chromosome or an autosome. In the absence of SRY, overexpression of other pro-testis genes, e.g. SOX family genes, or failure of pro-ovarian/anti-testis genes, such as WNT4 and RSPO1, may underlie the development of testicular tissue. Recent experimental and clinical evidence giving insight into SRY-negative 46,XX testicular or ovotesticular DSD is discussed.

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Cell fate commitment during mammalian sex determination

Cited by 99 publications

References 105 publications

FGF9, activin and TGFβ promote testicular characteristics in an XX gonad organ culture model

FGF9, activin and TGFβ promote testicular characteristics in an XX gonad organ culture model

Germline stem cells are critical for sexual fate decision of germ cells

Disorders of Sex Development with Testicular Differentiation in SRY-Negative 46,XX Individuals: Clinical and Genetic Aspects

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