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Developmentally programmed nuclear pore complex replacement enables oocyte specification

Venkat, S.; Nguyen, T.; Blangini, C.; Pollak, M.; Schindler, K.; Capelson, M.; Rangan, P.

2026-02-16 developmental biology
10.64898/2026.02.13.705775 bioRxiv
Show abstract

Oocytes endow embryos with molecular machinery essential for development, but not all maternal components are inherited indiscriminately. In Drosophila, surveillance pathways eliminate defective mitochondria and aberrant RNAs from the maternal pool. Whether stable nuclear structures, like nuclear pore complexes (NPCs), are similarly curated remains unknown. Here, we uncover a developmentally programmed NPC turnover pathway that renews NPCs during oocyte specification. NPC levels decline through a combination of passive dilution, driven by deferred nucleoporin expression, and active degradation mediated by the ESCRT-III/Vps4 pathway. This clearance is counterbalanced by subsequent de novo NPC synthesis. Failure to turn over NPCs results in aberrantly persistent germ cell gene expression and defective oocyte specification. These findings establish NPC renewal as a critical step in oocyte identity establishment and maternal provisioning.

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