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Communication Dans Un Congrès Année : 2012

Involvment of [i]DMRT1[/i] in XX sex-reversed polled goats

Résumé

In goats, the PIS (Polled Intersex Syndrome) mutation results in hornlessness of heterozygous (PIS+/-) and homozygous (PIS-/-) animals of both sexes, and to a female-to-male sex-reversal in XX animals homozygous for the mutation (XX PIS-/-). The PIS mutation is a regulatory mutation which corresponds to a 11.7 kb-deletion on goat chromosome 1, inducing a long-range transcriptional effect on FOXL2 and various non-coding RNAs [3-5]. For several years, we have accumulated evidences that these ncRNAs are involved in FOXL2 expression regulation [5, 1; see Pannetier et al. abstract], and we consider now that the sole "acting" gene of the PIS locus is FOXL2. Thus, in goats, the transcriptional silencing of FOXL2 in the early-developing XX PIS-/- gonad is responsible for testis formation in a female genetic context. In order to highlight new crucial genes for ovarian differentiation that could be FOXL2 target genes, we performed a high-throughput sequencing of transcripts from male (XY PIS+/+), female (XX PIS+/+) and sex-reversed (XX PIS-/-) gonads at 36 days post-coïtum (dpc), the key stage of gonadic switch in goats. At this stage, we previously showed that in the sex-reversed gonad, FOXL2 was not detected as expected, but SOX9 and in theory other male genes were not up-regulated yet [4]. Consequently, mis-regulated genes between XX sex-reversed gonad and normal ovary at this stage may be FOXL2 target genes and crucial actors of ovarian differentiation. The RNA-sequencing results confirmed by RT-qPCR, showed that FOXL2 inhibits testicular differentiation on top of being an activator of ovarian development. This inhibition takes place at three levels; first, FOXL2 represses androgens production, then, it protects XX germ cells fate by inhibiting CYP26b1 expression, and finally it represses Sertoli cells differentiation, by inhibiting the DMRT1 gene that should lead to SOX9 up-regulation. Indeed, our data show that DMRT1 is up-regulated in 36 dpc XX sex-reversed gonads whereas SOX9 remains expressed as in normal ovaries. As DMRT1 is considered as the testis determining factor in at least three species of non-mammalian vertebrates where SRY is absent [2, 7, 8], and because DMRT1 haplo-insufficiency is involved in XY male-to-female sex reversal in humans [6], its up-regulation in XX sex-reversed gonads suggests its primary involvement in SOX9 up-regulation during the PIS sex-reversal process in goats.

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Dates et versions

hal-01019618 , version 1 (07-07-2014)

Identifiants

  • HAL Id : hal-01019618 , version 1
  • PRODINRA : 254858

Citer

Maeva Elzaiat, Dominique Thepot Thépot, Luc Jouneau, Aurélie Allais-Bonnet, Christophe C. Klopp, et al.. Involvment of [i]DMRT1[/i] in XX sex-reversed polled goats. 6. International Symposium on the Biology of Vertebrate Sex Determination, Vertebrate-biosex. USA., Apr 2012, Kona, Hawai, United States. 1 p. ⟨hal-01019618⟩
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