Regulatory mechanism of developmental time by oscillator genes

2020 Fiscal Year Final Research Report

• Project Area: Interplay of developmental clock and extracellular environment in brain formation
• Project/Area Number: 16H06480
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: Kageyama Ryoichiro 京都大学, ウイルス・再生医科学研究所, 教授 (80224369)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: 神経幹細胞 / 発現振動 / Hes1 / Hes5 / Notch / 光遺伝学 / 分節時計 / Hes7

Outline of Final Research Achievements

Neural stem cells (NSCs) sequentially produce deep-layer neurons, superficial-layer neurons, and astrocytes by changing their differentiation competency. The exact mechanism of how the timing of these transitions is controlled remained to be analyzed. Here we found that Hes1 and Hes5 expression oscillates with a 2-3-hour periodicity in NSCs and that overexpression or inactivation of these genes accelerates or delays the transitions of NSC competency, respectively. Furthermore, dampened oscillations lead to microcephaly. We also found that stable oscillatory expression in NSCs and the segmentation clock depends on Notch signaling. These results suggest that the Notch-Hes1/Hes5 oscillators act as clock genes that regulate neural development.

Free Research Field

総合生物

Academic Significance and Societal Importance of the Research Achievements

発生過程の進行を制御する生物時計、いわゆる発生時計の実体は長らく不明であった。唯一の例外は、体節形成過程を制御する分節時計遺伝子Hes7である。神経発生過程では、神経幹細胞は決められたスケジュールに従って順番に深層ニューロン、浅層ニューロン、アストロサイトを産生する。本研究では、Hes7の相同遺伝子であるHes1やHes5がこの神経発生過程の進行を制御する発生時計であることを初めて明らかにした。