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Reconstitution of the oocyte nucleolus in mice through a single nucleolar protein, NPM2.

  • Ogushi, Sugako1, 2
  • Yamagata, Kazuo3
  • Obuse, Chikashi4
  • Furuta, Keiko5
  • Wakayama, Teruhiko3
  • Matzuk, Martin M6
  • Saitou, Mitinori2, 7, 8, 9
  • 1 The Hakubi Center for Advanced Research, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan [email protected] , (Japan)
  • 2 Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto 606-8501, Japan. , (Japan)
  • 3 Laboratory for Genomic Reprogramming, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. , (Japan)
  • 4 Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido 001-0021, Japan. , (Japan)
  • 5 Division of Electron Microscopic Study, Center for Anatomical Studies, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. , (Japan)
  • 6 Departments of Pathology & Immunology, Molecular and Cellular Biology, Molecular and Human Genetics, and Pharmacology, and Center for Drug Discovery, Baylor College of Medicine, Houston, Texas 77030, USA.
  • 7 Institute for Integrated Cell-Material Sciences, Kyoto University Institute for Advanced Study, Sakyo-ku, Kyoto 606-8501, Japan. , (Japan)
  • 8 JST, CREST/ERATO, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. , (Japan)
  • 9 Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. , (Japan)
Published Article
Journal of Cell Science
The Company of Biologists
Publication Date
Jul 15, 2017
DOI: 10.1242/jcs.195875
PMID: 28600324


The mammalian oocyte nucleolus, the most prominent subcellular organelle in the oocyte, is vital in early development, yet its key functions and constituents remain unclear. We show here that the parthenotes/zygotes derived from enucleolated oocytes exhibited abnormal heterochromatin formation around parental pericentromeric DNAs, which led to a significant mitotic delay and frequent chromosome mis-segregation upon the first mitotic division. A proteomic analysis identified nucleoplasmin 2 (NPM2) as a dominant component of the oocyte nucleolus. Consistently, Npm2-deficient oocytes, which lack a normal nucleolar structure, showed chromosome segregation defects similar to those in enucleolated oocytes, suggesting that nucleolar loss, rather than micromanipulation-related damage to the genome, leads to a disorganization of higher-order chromatin structure in pronuclei and frequent chromosome mis-segregation during the first mitosis. Strikingly, expression of NPM2 alone sufficed to reconstitute the nucleolar structure in enucleolated embryos, and rescued their first mitotic division and full-term development. The nucleolus rescue through NPM2 required the pentamer formation and both the N- and C-terminal domains. Our findings demonstrate that the NPM2-based oocyte nucleolus is an essential platform for parental chromatin organization in early embryonic development.

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