Developmentally programmed nuclear pore complex replacement enables oocyte specification

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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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-02-16
DOI
https://doi.org/10.64898/2026.02.13.705775
Primary Topic
Nuclear Structure and Function
Type
article
Field-Weighted Citation Impact
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article

Developmentally programmed nuclear pore complex replacement enables oocyte specification

Tram Nguyen, Karen Schindler, Prashanth Rangan, Shruti Raja Venkat et al.
bioRxiv (Cold Spring Harbor Laboratory)
Nuclear Structure and Function
article

Developmentally programmed nuclear pore complex replacement enables oocyte specification

Tram Nguyen, Karen Schindler, Prashanth Rangan, Shruti Raja Venkat, Cecilia Blangini, Michelle Pollak, Maya Capelson
article en

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.

bioRxiv (Cold Spring Harbor Laboratory)
Rutgers, The State University of New Jersey (US), San Diego State University (US), New York Stem Cell Foundation (US), Icahn School of Medicine at Mount Sinai (US)
Reduced inequalities
Openalex Percentile: Top 54%
Nuclear Structure and Function
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