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Regulation of Asymmetrical Cytokinesis by cAMP during Meiosis I in Mouse Oocytes

机译:cAMP在小鼠卵母细胞减数分裂I期间对不对称细胞分裂的调控

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摘要

Mammalian oocytes undergo an asymmetrical first meiotic division, extruding half of their chromosomes in a small polar body to preserve maternal resources for embryonic development. To divide asymmetrically, mammalian oocytes relocate chromosomes from the center of the cell to the cortex, but little is known about the underlying mechanisms. Here, we show that upon the elevation of intracellular cAMP level, mouse oocytes produced two daughter cells with similar sizes. This symmetrical cell division could be rescued by the inhibition of PKA, a cAMP-dependent protein kinase. Live cell imaging revealed that a symmetrically localized cleavage furrow resulted in symmetrical cell division. Detailed analyses demonstrated that symmetrically localized cleavage furrows were caused by the inappropriate central positioning of chromosome clusters at anaphase onset, indicating that chromosome cluster migration was impaired. Notably, high intracellular cAMP reduced myosin II activity, and the microinjection of phospho-myosin II antibody into the oocytes impeded chromosome migration and promoted symmetrical cell division. Our results support the hypothesis that cAMP plays a role in regulating asymmetrical cell division by modulating myosin II activity during mouse oocyte meiosis I, providing a novel insight into the regulation of female gamete formation in mammals.
机译:哺乳动物卵母细胞经历不对称的第一次减数分裂分裂,将其一半的染色体挤压在一个小的极体中,以保留母体资源以用于胚胎发育。为了不对称分裂,哺乳动物卵母细胞将染色体从细胞中心移至皮层,但对其潜在机制知之甚少。在这里,我们显示出随着细胞内cAMP水平的升高,小鼠卵母细胞产生了两个大小相似的子细胞。这种对称的细胞分裂可以通过抑制PKA(一种cAMP依赖性蛋白激酶)来挽救。活细胞成像显示对称的分裂沟导致对称的细胞分裂。详细的分析表明,对称分布的分裂沟是由于后期开始时染色体簇的中心定位不当引起的,这表明染色体簇的迁移受到了损害。值得注意的是,高细胞内cAMP降低了肌球蛋白II的活性,而磷酸肌球蛋白II抗体向卵母细胞的显微注射阻碍了染色体迁移并促进了对称的细胞分裂。我们的研究结果支持以下假设:cAMP在小鼠卵母细胞减数分裂I期间通过调节肌球蛋白II的活性在调节不对称细胞分裂中起作用,从而为哺乳动物雌配子形成的调控提供了新的见识。

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