RIKEN Center for Biosystems Dynamics Research Laboratory for Chromosome Segregation

Team Leader: Tomoya Kitajima (Ph.D.)

Japanese Page

Research Summary

Oocytes, female germ cells, mature into an egg through meiosis I, which is followed by meiosis II upon fertilization. The fertilized egg undergoes mitotic cell divisions to give rise to a complete body. Each cell division segregates chromosomes, which carry genetic information, into daughter cells. Correct chromosome segregation is essential for the development and maintenance of an organism. However, errors in chromosome segregation are common in oocytes and fertilized eggs. In particular, the error rate in oocytes increases with maternal age. These errors are a major cause of infertility, miscarriage, and congenital diseases such as Down syndrome. We will reveal mechanisms of chromosome segregation that operate for transgenerational genetic inheritance. We will also identify the causes of chromosome segregation errors. We will use advanced techniques for high-throughput and high-resolution live imaging of mouse oocytes and embryos, combined with micromanipulation and genetic engineering methods. Based on novel mechanisms to be identified, we will develop technologies to manipulate chromosome segregation, which will be used in collaborative studies with reproductive medicine.

Main Research Fields

Biology

Related Research Fields

Biological Sciences

Keywords

Chromosome
Meiosis
Oocyte
Egg, ova

Selected Publications

1. Asai K, Zhou Y, Takenouchi O, et al.:
"Artificial kinetochore beads establish a biorientation-like state in the spindle.”
Science, 385(6715), 1366-1375 (2024).
doi: 10.1126/science.adn5428.
2. Takahashi S, Kyogoku H, Hayakawa T, et al.:
"Embryonic genome instability upon DNA replication timing program emergence.”
Nature, 633, 686-694 (2024).
doi: 10.1038/s41586-024-07841-y.
3. Takenouchi O, Sakakibara Y, Kitajima TS.:
"Live chromosome identifying and tracking reveals size-based spatial pathway of meiotic errors in oocytes.”
Science, 385(6706), (2024).
doi: 10.1126/science.adn5529.
4. Mishina T, Tabata N, Hayashi T, et al.:
"Single-oocyte transcriptome analysis reveals aging-associated effects influenced by life stage and calorie restriction.”
Aging Cell, 20(8), e13428 (2021).
doi: 10.1111/acel.13428.
5. Courtois A, Yoshida S, Takenouchi O, et al.:
"Stable kinetochore–microtubule attachments restrict MTOC position and spindle elongation in oocytes.”
EMBO Reports, 22(4), e51400 (2021).
doi: 10.15252/embr.202051400.
6. Yoshida S, Nishiyama S, Lister L, et al.:
"Prc1-rich kinetochores are required for error-free acentrosomal spindle bipolarization during meiosis I in mouse oocytes.”
Nature Communications, 11(1), 2652 (2020).
doi: 10.1038/s41467-020-16488-y.
7. Ding Y, Kaido M, Llano E, et al.:
"The post-anaphase SUMO pathway ensures the maintenance of centromeric cohesion through meiosis I-II transition in mammalian oocytes.”
Current Biology, 28(10), 1661-1669 (2018).
doi: 10.1016/j.cub.2018.04.019.
8. Kyogoku H, Kitajima TS.：
"Large cytoplasm is linked to the error-prone nature of oocytes.”
Developmental Cell, 41(3), 287-298 (2017).
doi: 10.1016/j.devcel.2017.04.009.
9. Sakakibara Y, Hashimoto S, Nakaoka H, et al.:
"Bivalent separation into univalents precedes age-related meiosis I errors in oocytes.”
Nature Communications, 6, 7550 (2015).
doi: 10.1038/ncomms8550.
10. Yoshida S, Kaido M, Kitajima TS.:
"Inherent instability of correct kinetochore-microtubule attachments during meiosis I in oocytes.”
Developmental Cell, 33(5), 589–602 (2015).
doi: 10.1016/j.devcel.2015.04.020.