2022 Fiscal Year Final Research Report
Roles of extrinsic signals on fate choice of neural progenitor cells in the developing neocortex
Project/Area Number |
20K06868
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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 | The University of Tokyo |
Principal Investigator |
Sanada Kamon 東京大学, 大学院理学系研究科(理学部), 准教授 (50431896)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 大脳新皮質 / 神経細胞移動 / 細胞質ダイニン / AMP活性化キナーゼ |
Outline of Final Research Achievements |
During the mammalian brain development, neurons are born from neural progenitor cells and undergo neuronal migration to their final destination. These processes, neurogenesis and neuronal migration, are essential for neurodevelopment. However, the cell-extrinsic signals and their intracellular signaling pathways that govern neurogenesis and neuronal migration are poorly understood. In the present study, we show that AMP-activated protein kinase (AMPK) that is known to be activated by multiple extrinsic signals contributes to neuronal migration in the developing neocortex. In sum, we find that activated AMPK phosphorylates and positively regulates the cytoplasmic dynein to enhance forward movement of the nucleus and thereby neuronal migration. The present study thus uncovers a novel mechanism that regulates cytoplasmic dynein, a critical component for neuronal migration, and the molecular machinery of the interface between migratory neurons and their extracellular environment.
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Free Research Field |
神経科学
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Academic Significance and Societal Importance of the Research Achievements |
秩序正しい神経細胞移動は脳発生に極めて重要であり、この過程が障害されると脳発生異常が起こる。神経細胞移動において、ダイナミックな細胞骨格の変化やモーター分子の制御は必要不可欠であるが、その制御機構には謎が多い。本研究成果は、世界に先駆けて微小管モーターである細胞質ダイニンの制御機構を明らかにしている。また従来、神経細胞移動を制御する細胞外環境因子およびその細胞内情報伝達機構は充分に理解されておらず、本研究成果は、神経細胞移動という複雑なシステムを理解する上で、細胞外環境の重要性およびそのインターフェースの分子機構を提示しており、当該分野の将来の研究展開に大きな影響を及ぼすと自負している。
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