Nucleoporin107 mediates female sexual differentiation via Dsx

We recently identified a missense mutation in Nucleoporin107 (Nup107; D447N) underlying XX-ovarian-dysgenesis (XX-OD), a disorder characterized by underdeveloped and dysfunctional ovaries. Specific knockdown of Nup107 in the somatic gonadal cells and moreover, modelling of the human mutation in Drosophila result in ovarian-dysgenesis-like phenotypes in female flies. The aberrant phenotypes in larval and adult ovaries compromised for Nup107 are associated with hyperactivation of BMP signalling. Transcriptomic analysis identified the somatic sex-determination gene Doublesex (dsx) and the extracellular metalloprotease AdamTS-A as targets of Nup107.  Either loss or gain of Dsx in the gonadal soma is sufficient to respectively mimic or rescue the phenotypes induced by Nup107 loss. Furthermore, adamTS-A is transcriptionally regulated by Dsx, and its knockdown in the somatic gonad hyperactivates BMP signaling and to a large extent recapitulates loss of Nup107 phenotypes. Thus, Dsx acts downstream of Nup107 to impact female germline stem cells via sex-specific modulation of the BMP pathway. Transcriptome analysis of both wild-type and mutant-rescued Nup107-null Drosophila larval gonad samples, performed in triplicate, together with a single sample of yw control gonad analysis.