The nature and roles of cellular metabolism and energy in the regulation of neuronal chain migration
Project/Area Number |
20K06865
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 46010:Neuroscience-general-related
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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 – 2023-03-31
|
Project Status |
Granted (Fiscal Year 2021)
|
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)
|
Keywords | metabolic pathway / neuronal migration / bioenergetics / ATP sensor / Bioenergetics / metabolic pathways / Neuronal migration / chain 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.
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Outline of Annual Research Achievements |
This research has two objectives: (1) visualize and quantify the energy status of chain migrating neurons; (2) unravel the metabolic sources that fuel neuronal migration. For objective (1), while I have established a system to express genetically encoded ATP sensors (ATeam) in vivo and in vitro, progress in FRET-based imaging of intracellular ATP is hindered by technical difficulties. For objective (2), I have generated a mouse knockout line with deficiency in a transcription factor known to promote OXPHOS metabolic pathway during development. Phenotypic analysis of the mutant line has shown defects in neuronal migration and/or their termination of migration.
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Current Status of Research Progress |
Current Status of Research Progress
4: Progress in research has been delayed.
Reason
The progress of this study is delayed. The FRET-based ATP sensor imaging is delayed due to a broken down of a laser line of our common confocal imaging system and the time it took to replace the laser. Another reason that delayed this project is due to COVID-related family issues.
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Strategy for Future Research Activity |
(1)I will perform further phenotype analysis of the knockout mice generated to understand the defects in detail, including morphological changes, dendritic pattern and axon projection. As the knockout mice die at birth, I will also employ CRISPR/CAS9 mediated gene editing to knockout the gene of interest via local in utero electroporation and observe the effect in postnatal samples. (2)I will perform manipulation of metabolic pathways using pharmacological reagents and examine the consequences of such manipulations on chain neuronal migration using in vitro whole tissue culture system. (3)I will introduce the fluorescent ATP sensors into the migrating neurons and image ATP levels in both fixed and living conditions.
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Report
(2 results)
Research Products
(2 results)