Nucleoporin107 mediates female sexual differentiation via Dsx
- The Hebrew University, Israel
- Hebrew University Hadassah Medical School, Israel
- The Hadassah Hebrew University Medical Center, Israel
- Hadassah Hebrew University Medical Center, Israel
- Princeton University, United States
Abstract
We recently identified a missense mutation in Nucleoporin107 (Nup107; D447N) underlying XX-ovarian-dysgenesis, a rare disorder characterized by underdeveloped and dysfunctional ovaries. Modeling 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.
Data availability
All raw RNA-seq data, as well as software versions and parameters, have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE141094
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Nucleoproin 107 Mediates Femae Sexual Differentiation via DoublesexNCBI Gene Expression Omnibus, GSE141094.
Article and author information
Author details
Funding
Israel Science Foundation (1788/15)
- David Zangen
- Offer Gerlitz
Israel Science Foundation (2295/19)
- David Zangen
- Offer Gerlitz
National Institute of Health (093913)
- Girish Deshpande
Ministry of Science and Technology
- Tgst Levi
Ministry of Aliyah and Integration
- Tgst Levi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Shore et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Nucleoporin107 mediates female sexual differentiation via Dsx
eLife 11:e72632.
https://doi.org/10.7554/eLife.72632
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