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.
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
Nucleoproin 107 Mediates Femae Sexual Differentiation via DoublesexNCBI Gene Expression Omnibus, GSE141094.
- David Zangen
- Offer Gerlitz
- David Zangen
- Offer Gerlitz
- Girish Deshpande
- Tgst Levi
- Tgst Levi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Xin Chen, Johns Hopkins University, United States
- Received: July 29, 2021
- Preprint posted: August 16, 2021 (view preprint)
- Accepted: March 17, 2022
- Accepted Manuscript published: March 21, 2022 (version 1)
- Accepted Manuscript updated: March 21, 2022 (version 2)
- Accepted Manuscript updated: March 22, 2022 (version 3)
- Version of Record published: April 1, 2022 (version 4)
© 2022, Shore et al.
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In order to understand morphogenesis, it is necessary to know the material properties or forces shaping the living tissue. In spite of this need, very few in vivo measurements are currently available. Here, using the early Drosophila embryo as a model, we describe a novel cantilever-based technique which allows for the simultaneous quantification of applied force and tissue displacement in a living embryo. By analyzing data from a series of experiments in which embryonic epithelium is subjected to developmentally relevant perturbations, we conclude that the response to applied force is adiabatic and is dominated by elastic forces and geometric constraints, or system size effects. Crucially, computational modeling of the experimental data indicated that the apical surface of the epithelium must be softer than the basal surface, a result which we confirmed experimentally. Further, we used the combination of experimental data and comprehensive computational model to estimate the elastic modulus of the apical surface and set a lower bound on the elastic modulus of the basal surface. More generally, our investigations revealed important general features that we believe should be more widely addressed when quantitatively modeling tissue mechanics in any system. Specifically, different compartments of the same cell can have very different mechanical properties; when they do, they can contribute differently to different mechanical stimuli and cannot be merely averaged together. Additionally, tissue geometry can play a substantial role in mechanical response, and cannot be neglected.
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