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

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06865
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: National 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
• Keywords: Metabolic pathway / Chain migration / Esrrg / termination / ATP sensor

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.

Free Research Field

Developmental Neurobiology

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。