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WDR62 是参与小鼠卵母细胞减数分裂成熟过程中纺锤体迁移和不对称细胞分裂的新型参与者。

WDR62 is a novel participator in spindle migration and asymmetric cytokinesis during mouse oocyte meiotic maturation.

机构信息

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China; Department of Hubei Province Engineering Research Center in Buffalo Breeding and Products, Wuhan, 430070, Hubei, China.

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

出版信息

Exp Cell Res. 2020 Feb 1;387(1):111773. doi: 10.1016/j.yexcr.2019.111773. Epub 2019 Dec 10.

DOI:10.1016/j.yexcr.2019.111773
PMID:31836472
Abstract

In female meiosis, oocyte meiotic maturation is a form of asymmetric cell division, producing the first polar body and a large oocyte, in which the asymmetry of oocyte meiotic division depends on spindle migration and positioning, and cortical polarization. In this study, we conclude that WDR62 (WD40-repeat protein 62) plays an important role in asymmetric meiotic division during mouse oocyte maturation. Our initial study demonstrated that WDR62 mainly co-localized with chromosomes during mouse oocyte meiotic maturation. Interference of Wdr62 by siRNA microinjection did not affect germinal vesicle breakdown (GVBD) but compromised the first polar body extrusion (PBE) with the large polar bodies generated, which is coupled with a higher incidence of spindle abnormality and chromosome misalignment. Further analysis concluded that loss of WDR62 blocked asymmetric spindle positioning and actin cap formation, which should be responsible for large polar body extrusion. Moreover, WDR62 decline intervened with the Arp2/3 complex, an upstream regulator for the cortical actin. Besides for p-MAPK, a critical regulator for the asymmetric division of oocyte, WDR62-depleted oocytes showed perturbation only in localization pattern but not expression level. In summary, our study defines WDR62 as an essential cytoskeletal regulator of spindle migration and asymmetric division during mouse oocyte meiotic maturation.

摘要

在雌性减数分裂中,卵母细胞减数分裂成熟是一种不对称细胞分裂的形式,产生第一极体和一个大的卵母细胞,其中卵母细胞减数分裂的不对称性取决于纺锤体的迁移和定位以及皮质极化。在这项研究中,我们得出结论,WDR62(WD40 重复蛋白 62)在小鼠卵母细胞成熟过程中的不对称减数分裂中发挥重要作用。我们的初步研究表明,WDR62 在小鼠卵母细胞减数分裂成熟过程中主要与染色体共定位。用 siRNA 微注射干扰 Wdr62 不会影响生发泡破裂(GVBD),但会影响第一极体挤出(PBE),产生大的极体,这与更高的纺锤体异常和染色体错位发生率有关。进一步的分析得出结论,WDR62 的缺失阻止了不对称纺锤体定位和肌动蛋白帽的形成,这应该是导致大极体挤出的原因。此外,WDR62 的下降干预了 Arp2/3 复合物,这是皮质肌动蛋白的上游调节剂。除了 p-MAPK,它是卵母细胞不对称分裂的关键调节剂外,WDR62 耗尽的卵母细胞仅在定位模式上而不是表达水平上显示出扰动。总之,我们的研究将 WDR62 定义为小鼠卵母细胞减数分裂成熟过程中纺锤体迁移和不对称分裂的必需细胞骨架调节剂。

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