scholarly journals Nucleoporin107 mediates female sexual differentiation via Dsx

2021 ◽  
Author(s):  
Offer Gerlitz ◽  
Girish Deshpande ◽  
Tikva Shore ◽  
Tgst Levi

We recently identified a missense mutation in Nucleoporin107 (Nup107; D447N) underlying XX-ovarian-dysgenesis, a rare disorder characterized by underdeveloped and dysfunctional ovaries. Modelling of the human mutation in Drosophila or specific knockdown of Nup107 in the gonadal soma resulted in ovarian-dysgenesis-like phenotypes. Transcriptomic analysis identified the somatic sex-determination gene doublesex (dsx) as a target of Nup107. Establishing Dsx as a primary relevant target of Nup107, either loss or gain of Dsx in the gonadal soma is sufficient to mimic or rescue the phenotypes induced by Nup107 loss. Importantly, the aberrant phenotypes induced by compromising either Nup107 or dsx are reminiscent of BMP signaling hyperactivation. Remarkably, in this context, the metalloprotease AdamTS-A, a transcriptional target of both Dsx and Nup107, is necessary for the calibration of BMP signaling. As modulation of BMP signaling is a conserved critical determinant of soma-germline interaction, the sex and tissue specific deployment of Dsx-F by Nup107 seems crucial for the maintenance of the homeostatic balance between the germ cells and somatic gonadal cells.

Endocrinology ◽  
2021 ◽  
Author(s):  
Geneviève Jolivet ◽  
Nathalie Daniel-Carlier ◽  
Erwana Harscoët ◽  
Eloïse Airaud ◽  
Aurélie Dewaele ◽  
...  

Abstract AROMATASE is encoded by the CYP19A1 gene and is the cytochrome enzyme responsible for estrogen synthesis in vertebrates. In most mammals, a peak of CYP19A1 gene expression occurs in the fetal XX gonad when sexual differentiation is initiated. To elucidate the role of this peak, we produced three lines of TALEN genetically edited CYP19A1 KO rabbits, that were devoid of any estradiol production. All the KO XX rabbits developed as females with aberrantly small-sized ovaries in adulthood, an almost empty reserve of primordial follicles and very few large antrum follicles. Ovulation never occurred. Our histological, immunohistological and transcriptomic analyses showed that the estradiol surge in the XX fetal rabbit gonad is not essential to its determination as an ovary, or for meiosis. However, it is mandatory for the high proliferation and differentiation of both somatic and germ cells, and consequently for establishment of the ovarian reserve.


2020 ◽  
Author(s):  
Geneviève Jolivet ◽  
Nathalie Daniel-Carlier ◽  
Erwana Harscoët ◽  
Eloïse Airaud ◽  
Aurélie Dewaele ◽  
...  

AbstractAROMATASE, encoded by the CYP19A1 gene, is the cytochrome enzyme responsible for the synthesis of estrogens in vertebrates. In most mammals a peak of expression of the CYP19A1 gene occurs in the fetal XX gonad when sexual differentiation starts up. To elucidate the role of this peak, we produced 3 lines of TALEN genetically edited CYP19A1 KO rabbits, that were void of any production of estradiol. All KO XX rabbits developed as females, with aberrantly small sized ovaries at adulthood, an almost empty reserve of primordial follicles and very few large antrum follicles. Ovulation never occurred. Our histological, immunohistological and transcriptomic analyses showed that the surge of estradiol in the XX fetal rabbit gonad is dispensable for its determination as an ovary, or for meiosis. However, it is mandatory for the high proliferation and differentiation of both somatic and germ cells, and consequently for the establishment of the ovarian reserve.


Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5033-5048 ◽  
Author(s):  
J.H. Hager ◽  
T.W. Cline

With a focus on Sex-lethal (Sxl), the master regulator of Drosophila somatic sex determination, we compare the sex determination mechanism that operates in the germline with that in the soma. In both cell types, Sxl is functional in females (2X2A) and nonfunctional in males (1X2A). Somatic cell sex is determined initially by a dose effect of X:A numerator genes on Sxl transcription. Once initiated, the active state of SXL is maintained by a positive autoregulatory feedback loop in which Sxl protein insures its continued synthesis by binding to Sxl pre-mRNA and thereby imposing the productive (female) splicing mode. The gene splicing-necessary factor (snf), which encodes a component of U1 and U2 snRNPs, participates in this RNA splicing control. Here we show that an increase in the dose of snf+ can trigger the female Sxl RNA splicing mode in male germ cells and can feminize triploid intersex (2X3A) germ cells. These snf+ dose effects are as dramatic as those of X:A numerator genes on Sxl in the soma and qualify snf as a numerator element of the X:A signal for Sxl in the germline. We also show that female-specific regulation of Sxl in the germline involves a positive autoregulatory feedback loop on RNA splicing, as it does in the soma. Neither a phenotypically female gonadal soma nor a female dose of X chromosomes in the germline is essential for the operation of this feedback loop, although a female X-chromosome dose in the germline may facilitate it. Engagement of the Sxl splicing feedback loop in somatic cells invariably imposes female development. In contrast, engagement of the Sxl feedback loop in male germ cells does not invariably disrupt spermatogenesis; nevertheless, it is premature to conclude that Sxl is not a switch gene in germ cells for at least some sex-specific aspects of their differentiation. Ironically, the testis may be an excellent organ in which to study the interactions among regulatory genes such as Sxl, snf, ovo and otu which control female-specific processes in the ovary.


Parasitology ◽  
1972 ◽  
Vol 65 (1) ◽  
pp. 131-136 ◽  
Author(s):  
B. Klimes ◽  
D. G. Rootes ◽  
Zabel Tanielian

In chickens kidney-cell culture gametogony of E. tenella usually occurs in a limited number of selected cells in the form of nests of gametocytes. Some cells contain only macrogametocytes, others only microgametocytes and some cells contain both sexes together. Mixed nests of gametocytes are evidence for genetic sex determination. By using PAS staining the origin of macrogametocytes and microgametocytes can be retraced to the merozoites and schizonts of the last generation, which are differentiated by this technique.


1995 ◽  
Vol 6 (1) ◽  
pp. 87-95 ◽  
Author(s):  
A M Campbell ◽  
H J Rayala ◽  
U W Goodenough

Sexual differentiation in the heterothallic alga Chlamydomonas reinhardtii is controlled by two mating-type loci, mt+ and mt-, which behave as a pair of alleles but contain different DNA sequences. A mutation in the mt minus-linked imp11 gene has been shown previously to convert a minus gamete into a pseudo-plus gamete that expresses all the plus gametic traits except the few encoded by the mt+ locus. Here we describe the iso1 mutation which is unlinked to the mt- locus but is expressed only in minus gametes (sex-limited expression). A population of minus gametes carrying the iso1 mutation behaves as a mixture of minus and pseudo-plus gametes: the gametes isoagglutinate but they do not fuse to form zygotes. Further analysis reveals that individual gametes express either plus or minus traits: a given cell displays one type of agglutinin (flagellar glycoprotein used for sexual adhesion) and one type of mating structure. The iso1 mutation identifies a gene unlinked to the mating-type locus that is involved in sex determination and the repression of plus-specific genes.


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