Initial spindle positioning at the oocyte center protects against incorrect kinetochore-microtubule attachment and aneuploidy in mice.

Initial spindle positioning at the oocyte center protects against incorrect kinetochore-microtubule attachment and aneuploidy in mice.
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DOI:
10.1126/sciadv.add7397
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发表时间:
2023-02-17
期刊:
影响因子:
13.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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纺锤体在卵母细胞内的定位必须严格调节。在小鼠中,纺锤体主要在卵母细胞中心组装,然后向皮质迁移以实现高度不对称分裂,这是雌性减数分裂的特征。主轴的初始中心定位的意义在很大程度上是未知的。我们发现,初始纺锤体定位在卵母细胞中心是一种保险机制,以避免过早暴露的纺锤体皮质CDC 42信号,干扰适当的kinetochore-microtubule附件,导致形成非整倍体配子。这些发现有助于理解为什么女性配子与非整倍体的高发生率有关,非整倍体是流产和先天性异常的主要遗传原因。纺锤体最初位于卵母细胞皮质附近会增加非整倍体的风险。
Spindle positioning within the oocyte must be tightly regulated. In mice, the spindle is predominantly assembled at the oocyte center before its migration toward the cortex to achieve the highly asymmetric division, a characteristic of female meiosis. The significance of the initial central positioning of the spindle is largely unknown. We show that initial spindle positioning at the oocyte center is an insurance mechanism to avoid the premature exposure of the spindle to cortical CDC42 signaling, which perturbs proper kinetochore-microtubule attachments, leading to the formation of aneuploid gametes. These findings contribute to understanding why female gametes are notoriously associated with high rates of aneuploidy, the leading genetic cause of miscarriage and congenital abnormalities. Initial positioning of the spindle near the oocyte cortex increases the risk of aneuploidy.
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