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Gonadal differentiation in mammals: the goat as an alternative model

Abstract : Since the discovery of SRY in 1990 and the demonstration that this gene is the Testis-Determining Factor in mammals, many studies focused on testis differentiation. Among these, the crucial role of SOX9 has been demonstrated in different vertebrate species. Moreover testis differentiating molecules such as FGF9 or PGD2 has been shown to be involved in the key process of SOX9 up-regulation in the XY developing gonads. More recently, key ovarian differentiating genes has been discovered in more or less masculinized XX sex-reversed females of different mammalian species. FOXL2 in the goat PIS syndrome, RSPO1 in a human syndrome and Wnt4 in mouse are genes belonging to this last category. Furthermore, recent studies revealed the existence of a balance between the male and the female genetic pathways and increasing studies aim to decipher gene interactions sustaining the fate of testis and ovary differentiation. In goat, mutation affecting expression of genes from the PIS locus (Polled Intersex Syndrome) is responsible for complete female-to-male sex-reversal. By positional cloning, we have demonstrated that the PIS mutation is an 11.7-kb regulatory-deletion affecting the transcriptional expression of three genes: two non-coding RNA, PISRT1 and PFOXic and one transcription factor, FOXL2. The transcriptional extinction of these three genes leads to testis formation in XX homozygous PIS-/- mutants. Since the discovery of this mutation in 2001, progresses have been made in order to understand the molecular functioning of this complex locus and the role of the different PIS-regulated genes in sex differentiation. Moreover, goat ovarian differentiation was studied at the early stages of development. Before meiotic stages, molecular and histological analyses revealed the existence of an ovarian specific organisation with a cortical part mainly composed of germ cells and a medullar part containing steroidogenically active somatic cells. Interestingly, the two main genes for ovarian development are specific of one of both compartments: RSPO1 is expressed in the cortex and FOXL2 in the medulla, showing that, in goat, these genes control two different pathways in the early female gonad development.
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https://hal.inrae.fr/hal-02812801
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Submitted on : Saturday, June 6, 2020 - 11:00:03 AM
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  • HAL Id : hal-02812801, version 1
  • PRODINRA : 34133

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Eric Pailhoux. Gonadal differentiation in mammals: the goat as an alternative model. Séminaire de l'IGMC, Nov 2009, Strasbourg, France. n.p. ⟨hal-02812801⟩

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