Establishment of Circadian ordering system during the developmental process in mammals

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02664
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yagita Kazuhiro 京都府立医科大学, 医学(系)研究科(研究院), 教授 (90324920)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 概日リズム / 生物時計 / 概日時計 / 発生 / 多能性幹細胞 / 細胞分化 / 体節時計 / リズム干渉

Outline of Final Research Achievements

It has been revealed that circadian clocks do not exist during early developmental stages. To date, we have succeeded in recapitulating the development of the circadian clock in vitro using pluripotent stem cells, a significant achievement. In this study, we concentrated on the mechanism of the generation of circadian time order during mammalian development, which is associated with the formation of an internal clock. In particular, we focused on the significance of the suppression of circadian clock development until organogenesis. The establishment of a mouse embryonic stem cell differentiation induction system and an embryonic organoid, designated the Gastruloid system, has permitted the clarification of the possibility that the circadian clock may interfere with the rhythm of somitogenesis. Furthermore, the study has yielded new insights into the physiological significance of circadian clock suppression during the early developmental stage.

Free Research Field

環境生理学、時間生物学

Academic Significance and Societal Importance of the Research Achievements

胎児期の前半までは脊椎動物としての基本的な体のパターンを形成する体節形成などが見られる。この時期、機能せず抑制されている体内時計の鍵因子を体節形成期に強制的に発現することで、体節時計に干渉し体節形成を阻害することが明らかになった。本研究によって、発生過程において体節形成の完了まで母体の概日リズムの伝達阻止も含め厳密に体内時計を抑制することは、正常な発生プロセスにおいて極めて重要な生理学的意義がある可能性が示唆された。