Nucleoporin107 mediates female sexual differentiation via Dsx

Tikva Shore, Tgst Levi, Rachel Kalifa, Amatzia Dreifuss, Dina Rekler, Ariella Weinberg-Shukron, Yuval Nevo, Tzofia Bialistoky, Victoria Moyal, Merav Yaffa Gold, Shira Leebhoff, David Zangen, Girish Deshpande, Offer Gerlitz

Research output: Contribution to journalArticlepeer-review


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 bone morphogenetic protein (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.

Original languageAmerican English
Article numbere72632
StatePublished - 21 Mar 2022

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology
  • General Neuroscience


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