Mechanisms of minor pole-mediated spindle bipolarization in human oocytes

• 成果类型: Article
• 署名作者: Wu, Tianyu; Luo, Yuxi; Zhang, Meiling; Chen, Biaobang; Du, Xingzhu; Gu, Hao; Xie, Siyuan; Pan, Zhiqi; Yu, Ran; Hai, Ruiqi; Niu, Xiangli; Hao, Guimin; Jin, Liping; Shi, Juanzi; Sun, Xiaoxi; Kuang, Yanping; Li, Wen; Sang, Qing; Wang, Lei
• 署名单位: Fudan University; Shanghai Jiao Tong University; Shanghai Jiao Tong University; Fudan University; Shanghai Academy of Science & Technology; Fudan University; Fudan University; Shanghai Jiao Tong University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11805
• DOI: 10.1126/science.ado1022
• 发表日期: 2024-08-23
• 关键词: chromosome segregation; microtubule generation; centrosome function; self-organization; mitotic spindle; augmin; aneuploidy; kif18a; localization; proteins

摘要

Spindle bipolarization, the process of a microtubule mass transforming into a bipolar spindle, is a prerequisite for accurate chromosome segregation. In contrast to mitotic cells, the process and mechanism of spindle bipolarization in human oocytes remains unclear. Using high-resolution imaging in more than 1800 human oocytes, we revealed a typical state of multipolar intermediates that form during spindle bipolarization and elucidated the mechanism underlying this process. We found that the minor poles formed in multiple kinetochore clusters contribute to the generation of multipolar intermediates. We further determined the essential roles of HAUS6, KIF11, and KIF18A in spindle bipolarization and identified mutations in these genes in infertile patients characterized by oocyte or embryo defects. These results provide insights into the physiological and pathological mechanisms of spindle bipolarization in human oocytes.