Laboratory for Chromosome Segregation, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, 650-0047, Japan.
Graduate School of Biostudies, Kyoto University, 606-8501, Kyoto, Japan.
Nat Commun. 2020 May 27;11(1):2652. doi: 10.1038/s41467-020-16488-y.
Acentrosomal meiosis in oocytes represents a gametogenic challenge, requiring spindle bipolarization without predefined bipolar cues. While much is known about the structures that promote acentrosomal microtubule nucleation, less is known about the structures that mediate spindle bipolarization in mammalian oocytes. Here, we show that in mouse oocytes, kinetochores are required for spindle bipolarization in meiosis I. This process is promoted by oocyte-specific, microtubule-independent enrichment of the antiparallel microtubule crosslinker Prc1 at kinetochores via the Ndc80 complex. In contrast, in meiosis II, cytoplasm that contains upregulated factors including Prc1 supports kinetochore-independent pathways for spindle bipolarization. The kinetochore-dependent mode of spindle bipolarization is required for meiosis I to prevent chromosome segregation errors. Human oocytes, where spindle bipolarization is reportedly error prone, exhibit no detectable kinetochore enrichment of Prc1. This study reveals an oocyte-specific function of kinetochores in acentrosomal spindle bipolarization in mice, and provides insights into the error-prone nature of human oocytes.
中心体缺失的减数分裂在卵母细胞中代表了一种配子发生的挑战，需要纺锤体的两极化而没有预先确定的两极化线索。虽然人们已经了解了促进无中心体微管核形成的结构，但对于介导哺乳动物卵母细胞纺锤体两极化的结构了解较少。在这里，我们表明在小鼠卵母细胞中，动粒对于减数分裂 I 中的纺锤体两极化是必需的。通过 Ndc80 复合物，卵母细胞特异性的、微管非依赖性的动粒上的平行微管交联蛋白 Prc1 的富集促进了这一过程。相比之下，在减数分裂 II 中，包含上调因子的细胞质，包括 Prc1，支持动粒非依赖性的纺锤体两极化途径。动粒依赖性的纺锤体两极化模式对于防止减数分裂 I 中的染色体分离错误是必需的。据报道，人类卵母细胞中纺锤体两极化容易出错，但其动粒上没有检测到 Prc1 的明显富集。这项研究揭示了小鼠中动粒在无中心体纺锤体两极化中的卵母细胞特异性功能，并深入了解了人类卵母细胞易错的本质。
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