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

First Author  Ogushi S Year  2017
Journal  J Cell Sci Volume  130
Issue  14 Pages  2416-2429
PubMed ID  28600324 Mgi Jnum  J:249486
Mgi Id  MGI:5922729 Doi  10.1242/jcs.195875
Citation  Ogushi S, et al. (2017) Reconstitution of the oocyte nucleolus in mice through a single nucleolar protein, NPM2. J Cell Sci 130(14):2416-2429
abstractText  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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