| Project/Area Number |
18K06508
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 46020:Anatomy and histopathology of nervous system-related
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| Research Institution | Gifu Pharmaceutical University (2021)
Keio University (2018) |
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Principal Investigator |
Honda Takao 岐阜薬科大学, 薬学部, 准教授 (30365225)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | Reelin / Dab1 / reeler / yotari / 大脳新皮質 / 辺縁帯 / Layer 1 / 層形成 / Layer1 |
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| Outline of Final Research Achievements |
Reelin is a secreted protein and regulates neuronal migration through a cytoplasmic protein Dab1. Mutation in the reelin or the dab1 gene causes a severe neuronal migration failure of excitatory neurons and lack of marginal zone (future layer 1). Although the Reelin-Dab1 signaling pathway regulates the neuronal migration, it has been unclear whether the lack of marginal zone/layer 1 is caused secondarily by the failure of neuronal migration. To examine whether the Reelin-Dab1 signaling pathway directry regulate layer 1 formation, we conditionally knocked out the dab1 gene when the excitatory neurons finished their migration. As a result, we observed a lack of layer 1, suggeting that the Dab1 signaling pathway directly regulates the maintenance of the layer 1.
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| Academic Significance and Societal Importance of the Research Achievements |
大脳新皮質は運動や感覚の最上位中枢が存在し意思決定等が行われる重要部位です。大脳新皮質は胎生期における大規模な神経細胞移動で形成されますが、その移動過程には脳表から分泌されるReelinと神経細胞内のDab1が必須で、reelinやdab1を欠損した場合、神経細胞の移動障害以外に脳表層にあるLayer1が消失します。Reelin-Dab1シグナルが神経細胞移動を制御することから、二次的にLayer1消失が生じた可能性が残されていましたが、本研究でDab1がLayer1の維持に直接関与することを明らかにしました。Layer1は認知機構制御を行う重要部位でその維持機構の一端が明らかになりました。
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