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The nature and roles of cellular metabolism and energy in the regulation of neuronal chain migration

Research Project

Project/Area Number 20K06865
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionNational Institute of Genetics

Principal Investigator

Zhu Yan  国立遺伝学研究所, 遺伝形質研究系, 助教 (50464235)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsMetabolic pathway / Chain migration / Esrrg / termination / ATP sensor / chain migration / precerebellar neurons / OXPHOS / tangential / radial / adhesion / protease / Precerebellar neurons / Metabolic pathways / metabolic pathway / neuronal migration / bioenergetics / Bioenergetics / metabolic pathways / Neuronal migration / energy status / energy sensor
Outline of Research at the Start

All cellular activities consume energy which is supplied by metabolic pathways. Status of energy consumption both reflects and controls cell behaviors. This research investigates the dynamics of energy status and the metabolic pathways during the development of mammalian brains.

Outline of Final Research Achievements

The objective of this research is to understand the energy expenditure and metabolic sources of chain migrating neurons, using the migrating precerebellar neurons in mouse hindbrain as a model. Based on our previous RNA-seq experiment, we hypothesized that a switch of metabolic pathways might affect neurons’ transition from migratory to stationary phases. To test this hypothesis, we generated a mouse line knocked out of the estrogen related receptor gamma (Esrrg) gene. Esrrg had previously been suggested to mediate the switch from glycolysis to OXPHOS. We found that a significant number of precerebellar neurons appeared to over-migrate, failing to terminate in ventral hindbrains, which supports our hypothesis. A second line of research was to measure the energy status of migrating neurons using a fluorescence ATP sensor. However, progress has been hampered by technical difficulties causing us to change the type of ATP sensor recently.

Academic Significance and Societal Importance of the Research Achievements

神経細胞の移動と適切な終止は神経回路の形成に重要です。従来の研究は、ガイダンス、接着、細胞骨格の観点から神経細胞の移動を理解することに焦点を当てていましたが、本研究では神経細胞の移動と代謝経路の関係に注目しました。この側面はほとんど研究されていません。私たちの結果は有望であり、将来の詳細な研究への道を開きます。また、細胞代謝は環境と密接に関連しているため、この研究は代謝障害が神経細胞の移動にどのように影響するかを理解するための基礎も提供します。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2024 2023 2022 2021 2020

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] A global gene regulatory program and its region-specific regulator partition neurons into commissural and ipsilateral projection types2024

    • Author(s)
      Aki Masuda, Kazuhiko Nishida, Rieko Ajima, Yumiko Saga, Marah Bakhtan, Avihu Klar, Tatsumi Hirata, Yan Zhu
    • Journal Title

      Science Advances

      Volume: 10 Issue: 21

    • DOI

      10.1126/sciadv.adk2149

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chemokine receptor CXCR7 non-cell-autonomously controls pontine neuronal migration and nucleus formation2020

    • Author(s)
      Zhu Yan、Hirata Tatsumi、Mackay Fabienne、Murakami Fujio
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 11830-11830

    • DOI

      10.1038/s41598-020-68852-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Uncovering a novel global transcriptional program and its interaction with local gene regulatory network for the specification of commissural neurons2023

    • Author(s)
      Yan Zhu
    • Organizer
      46th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2023 Annual Research Report
  • [Presentation] A global transcriptional program that specifies axon laterality in commissural neurons2022

    • Author(s)
      Yan Zhu
    • Organizer
      International Symposium: Development and Plasticity of the Brain
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] NHLH-1 & -2, a pair of highly related bHLH transcriptional factors, synergistically control the expression of Robo3 in mouse precerebellar neurons2021

    • Author(s)
      Yan Zhu
    • Organizer
      Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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