Department of Cell and Molecular Biology, Karolinska Institutet, Berzelius väg 35, 171 77 Stockholm, Sweden.
Nat Commun. 2014 Jul 9;5:4409. doi: 10.1038/ncomms5409.
The chromosome segregation process in human oocytes is highly error-prone, generating meiosis II (MII) oocytes with unbalanced chromatids that contribute to aneuploidy in offspring. This raises questions regarding the mechanism for transmission of chromatids and how chromatids evade the error correction mechanisms in MII oocytes. Here, we analyse the behaviour of chromatids in mouse MII oocytes. We find that chromatids align at the spindle equator at the metaphase stage of MII and that their presence does not obstruct entry into the anaphase stage. The alignment process is mediated by merotelic (bi-directional) microtubule-kinetochore attachments, revealing a multi-domain organization of the kinetochore of mammalian meiotic chromosomes. Our results suggest that biorientation of chromatids stabilize microtubule attachments at the kinetochores in a tension-dependent manner. Our results also suggest that merotelic attachments contribute to chromosome mis-segregation in wild-type MII oocytes. Thus, merotely is an important promoter of aneuploidy in mammalian oocytes.
人类卵母细胞的染色体分离过程极易出错,产生非整倍体的减数分裂 II(MII)卵母细胞。这引发了关于染色体传递机制以及染色体如何逃避 MII 卵母细胞中错误纠正机制的问题。在这里,我们分析了小鼠 MII 卵母细胞中染色体的行为。我们发现,在 MII 的中期,染色体在纺锤体赤道处排列,其存在并不妨碍进入后期。排列过程由微管-动粒的桥联(双向)附着介导,揭示了哺乳动物减数分裂染色体动粒的多域组织。我们的结果表明,染色体的双定向稳定了动粒处微管的附着,这是一种依赖张力的方式。我们的结果还表明,桥联附着有助于野生型 MII 卵母细胞中的染色体错误分离。因此,桥联是哺乳动物卵母细胞非整倍体的一个重要促进因素。