卵子の染色体は外側ほど気難しい~染色体分配の準備に潜む紡錘体内の空間差を発見~

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2025-08-20 理化学研究所,九州大学

理化学研究所と九州大学の共同研究グループは、卵母細胞の減数分裂において、染色体分配を担うモータータンパク質KIF11の必要量が紡錘体内の位置によって異なることを発見しました。マウス卵母細胞を用いた解析により、KIF11の量が半分以下になると紡錘体の伸長が阻害され、特に外側に位置する染色体が両方向性を確立できないことが判明しました。さらに、外側の染色体は微小管との誤接続(メロテリック接続)が多発しやすく、KIF11がその修正に寄与することも明らかになりました。これにより、染色体の正常な分配には紡錘体外側で特に高いKIF11依存性があることが示されました。本成果は卵子の染色体数異常の原因解明や、不妊症診断・治療法の開発に役立つと期待され、科学誌『EMBO Reports』に掲載されました。

卵子の染色体は外側ほど気難しい~染色体分配の準備に潜む紡錘体内の空間差を発見~

マウス卵母細胞における染色体の両方向性の確立におけるKIF11の空間的な必要量の違い

<関連情報>

Kif11半欠損卵母細胞は染色体二極化に空間的に異なる要件を示す Kif11-haploinsufficient oocytes reveal spatially differential requirements for chromosome biorientation

Tappei Mishina, Aurélien Courtois, Shuhei Yoshida, Kohei Asai, Hiroshi Kiyonari, and Tomoya S Kitajima,
EMBO Reports  Published:20 August 2025
DOI:https://doi.org/10.1038/s44319-025-00539-w

Abstract

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.

Synopsis

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This study reveals the necessity of biallelic functional Kif11 for bipolar spindle assembly in acentrosomal oocytes and a spatially differential requirement for homologous chromosome biorientation within the spindle.

  • Haploinsufficiency of Kif11 causes spindle assembly defects in mouse oocytes.
  • Partially bipolarized spindles in Kif11-haploinsufficient oocytes allow chromosome biorientation in the inner region of the equator, but not in the outer region.
  • Merotelic kinetochore-microtubule attachment is more likely to form in the outer region.
  • Requirement of KIF11 dosage for chromosome biorientation differs spatially in the oocyte spindle.
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