卵子へ染色体を正しく分配する手順~動原体が安全な手順での染色体分配を準備する~

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2025-06-04 理化学研究所

理化学研究所の研究チームは、哺乳類の卵母細胞における染色体の正確な分配手順を解明しました。卵母細胞は中心体を持たず、染色体を分配する紡錘体がゆっくりと二極性化されます。研究では、動原体に局在するリン酸化酵素MPS1が、紡錘体の二極性化を制御し、その後に微小管との接続を安定化させることが明らかになりました。MPS1を阻害すると紡錘体の二極性化が遅れ、染色体分配異常の原因となる誤った微小管の接続が増加します。この発見は、卵母細胞における染色体分配異常の原因解明や不妊治療への応用が期待されます。研究成果は2025年6月4日付で『The EMBO Journal』に掲載されました。

卵子へ染色体を正しく分配する手順~動原体が安全な手順での染色体分配を準備する~
マウス卵母細胞において紡錘体の二極性化を促進するMPS1

<関連情報>

MPS1は紡錘体の二極化をタイミングよく促進し、卵母細胞における動原体と微小管の接着エラーを防ぐ MPS1 promotes timely spindle bipolarization to prevent kinetochore-microtubule attachment errors in oocytes

Shuhei Yoshida, Reiko Nakagawa, Kohei Asai, and Tomoya S Kitajima
The EMBO Journal  Published:4 June 2025
DOI:https://doi.org/10.1038/s44318-025-00461-w

Abstract

Incorrect kinetochore–microtubule attachment leads to chromosome segregation errors. The risk of incorrect attachment is high in acentrosomal oocytes, where kinetochores are surrounded by randomly oriented microtubules until spindle bipolarization. Regulation of the temporal relationship between acentrosomal spindle bipolarization and kinetochore–microtubule attachment is unknown. Here, we show that in mouse oocytes, MPS1, a kinase more active at kinetochores with less stable microtubule attachment, promotes timely spindle bipolarization before kinetochores stably attach to microtubules. In MPS1-inhibited oocytes, spindle bipolarization is delayed and depends on microtubules stably attached to kinetochores, resulting in incorrect attachments. We propose a two-step kinetochore-based model where unstable and stable attachment states act sequentially for acentrosomal spindle assembly to reduce the risk of egg aneuploidy.

Synopsis

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Meiotic errors in oocytes cause egg aneuploidy. This study shows that kinetochores employ MPS1 kinase to promote timely spindle bipolarization before stable microtubule attachments in acentrosomal mammalian oocytes, reducing meiotic errors.
•The kinetochore kinase MPS1 promotes spindle bipolarization before stable kinetochore-microtubule attachment.
•MPS1 promotes spindle bipolarization via the kinetochore protein heterodimer NDC80-NUF2 and the anti-parallel microtubule cross-linker PRC1.
•MPS1-mediated timely spindle bipolarization prevents kinetochore-microtubule attachment errors.
•A two-step kinetochore-based mechanism, where unstable and stable attachment states act sequentially for acentrosomal spindle assembly, reduces the risk of egg aneuploidy.
細胞遺伝子工学
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