Center for Interdisciplinary Research in Biology (CIRB) College de France, CNRS, INSERM, PSL Research University, Equipe labellisée FRM, Paris, France.
International Institute of Molecular and Cell Biology, Warsaw, Poland.
EMBO Rep. 2018 Feb;19(2):368-381. doi: 10.15252/embr.201745225. Epub 2018 Jan 12.
Mitotic spindles assemble from two centrosomes, which are major microtubule-organizing centers (MTOCs) that contain centrioles. Meiotic spindles in oocytes, however, lack centrioles. In mouse oocytes, spindle microtubules are nucleated from multiple acentriolar MTOCs that are sorted and clustered prior to completion of spindle assembly in an "inside-out" mechanism, ending with establishment of the poles. We used HSET (kinesin-14) as a tool to shift meiotic spindle assembly toward a mitotic "outside-in" mode and analyzed the consequences on the fidelity of the division. We show that HSET levels must be tightly gated in meiosis I and that even slight overexpression of HSET forces spindle morphogenesis to become more mitotic-like: rapid spindle bipolarization and pole assembly coupled with focused poles. The unusual length of meiosis I is not sufficient to correct these early spindle morphogenesis defects, resulting in severe chromosome alignment abnormalities. Thus, the unique "inside-out" mechanism of meiotic spindle assembly is essential to prevent chromosomal misalignment and production of aneuploidy gametes.
有丝分裂纺锤体由两个中心体组装而成，中心体是含有中心粒的主要微管组织中心（MTOC）。然而，卵母细胞中的减数分裂纺锤体没有中心粒。在小鼠卵母细胞中，纺锤体微管由多个无中心粒的 MTOC 起始，这些 MTOC 在完成纺锤体组装之前进行分拣和聚集，采用“内到外”的机制，最终建立两极。我们使用 HSET（驱动蛋白-14）作为工具将减数分裂纺锤体组装推向有丝分裂的“外到内”模式，并分析了对分裂准确性的影响。我们表明，HSET 水平在减数分裂 I 中必须严格控制，即使 HSET 的轻微过表达也会迫使纺锤体形态发生更类似于有丝分裂：快速的纺锤体两极化和极体组装，同时伴随着焦点极体。减数分裂 I 的独特长度不足以纠正这些早期的纺锤体形态发生缺陷，导致严重的染色体排列异常。因此，减数分裂纺锤体组装的独特“内到外”机制对于防止染色体错位和产生非整倍体配子至关重要。
