Elucidation of the cause of changes in the frequency of chromosome segregation error during early embryonic development

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K15811
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Kobe University (2020); Institute of Physical and Chemical Research (2019)
• Principal Investigator: Kyogoku Hirohisa 神戸大学, 農学研究科, 助教 (20726038)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 卵母細胞 / 初期胚 / 微小管 / 紡錘体 / 細胞サイズ

Outline of Final Research Achievements

During cell division, a set of chromosomes must be evenly segregated to two daughter cells. In oocytes and early embryos, however, chromosomes frequently undergo segregation errors. Why chromosome segregation in oocytes and early embryos is error-prone remains poorly understood. In this study, we show that artificial reduction of cytoplasmic size can increase the stability of the spindle. Measurement of the stability of spindle microtubules using photoactivatable-GFP tubulin revealed that cytoplasmic reduction increased spindle stability, whereas cytoplasmic enlargement decreased. These effects were mediated by changes in the nuclear-to-cytoplasmic (N/C) ratio. These results suggest that the large cytoplasmic size in oocytes lowers spindle stability by reducing the N/C ratio. Moreover, we identified microtubule stabilizer.

Free Research Field

生殖生物学・発生工学

Academic Significance and Societal Importance of the Research Achievements

近年，哺乳類の卵母細胞の減数第一分裂や初期の胚発生過程においては，染色体が不均等に分配される頻度がほかの分裂に比べ非常に高く，このような染色体の分配異常が，ダウン症など重篤な先天性疾患や不妊の主要な原因と考えられている。この不均等分配の頻度は母体の年齢に大きく影響を受けることが分かっており，そのリスクは現代社会における少子化の一因であるとも考えられるが，なぜ卵母細胞や初期胚において染色体の不均等分配の頻度が高いのかは長い間わかっていない。本研究成果は，これらの疑問の一部にこたえられるものである。