Mishina Tappei, Courtois Aurélien, Yoshida Shuhei, Asai Kohei, Kiyonari Hiroshi, Kitajima Tomoya S
Laboratory for Chromosome Segregation, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan.
Faculty of Agriculture, Kyushu University, Fukuoka, Japan.
EMBO Rep. 2025 Aug 20. doi: 10.1038/s44319-025-00539-w.
Bipolar spindle assembly and chromosome biorientation are prerequisites for chromosome segregation during cell division. The kinesin motor KIF11 (also widely known as Eg5) drives spindle bipolarization by sliding antiparallel microtubules bidirectionally, elongating a spherical spindle into a bipolar-shaped structure in acentrosomal oocytes. During meiosis I, this process stretches homologous chromosome pairs, establishing chromosome biorientation at the spindle equator. The quantitative requirement for KIF11 in acentrosomal spindle bipolarization and homologous chromosome biorientation remains unclear. Here, using a genetic strategy to modulate KIF11 expression levels, we show that Kif11 haploinsufficiency impairs spindle elongation, leading to the formation of a partially bipolarized spindle during meiosis I in mouse oocytes. While the partially bipolarized spindle allows chromosome stretching in the inner region of its equator, it fails to do so in the outer region, where merotelic kinetochore-microtubule attachments are favored to form. These findings demonstrate the necessity of biallelic functional Kif11 for bipolar spindle assembly in acentrosomal oocytes and reveal a spatially differential requirement for homologous chromosome biorientation within the spindle.
双极纺锤体组装和染色体双定向是细胞分裂过程中染色体分离的前提条件。驱动蛋白KIF11（也被广泛称为Eg5）通过双向滑动反向平行微管来驱动纺锤体双极化，在无中心体的卵母细胞中将球形纺锤体拉长为双极形结构。在减数分裂I期间，这一过程拉伸同源染色体对，在纺锤体赤道处建立染色体双定向。KIF11在无中心体纺锤体双极化和同源染色体双定向中的定量需求仍不清楚。在这里，我们使用一种遗传策略来调节KIF11的表达水平，结果表明Kif11单倍体不足会损害纺锤体伸长，导致小鼠卵母细胞在减数分裂I期间形成部分双极化的纺锤体。虽然部分双极化的纺锤体允许其赤道内部区域的染色体拉伸，但在外部区域却无法做到，而外部区域有利于形成着丝粒微管错向连接。这些发现证明了双等位基因功能性Kif11对于无中心体卵母细胞中双极纺锤体组装的必要性，并揭示了纺锤体内同源染色体双定向在空间上的差异需求。
