| Project/Area Number |
18K06842
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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 48010:Anatomy-related
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 大脳新皮質 / 層構造 / Reelin / N-カドヘリン / 神経細胞 / 細胞凝集 / リーリン / 脂質ラフト / Dab1 / Dbnl / 発生 |
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| Outline of Final Research Achievements |
In the developing mammalian neocortex, neurons born in or near the ventricular zone migrate to just beneath the Marginal Zone below the brain surface, and then they subsequently accumulate with each other. In this study, we aimed to elucidate the molecular mechanism of this neuronal accumulation.
We identified cellular adhesion-related molecules that function downstream of the secreted protein Reelin, and found that their translocation into lipid rafts leads to N-cadherin-dependent cellular adhesion. We also examined a Reelin point mutant found in a pachygyria patient in terms of the extracellular secretory ability, receptor binding affinity, and effects on Reelin-induced neuronal aggregate formation, and clarified the cause of the dysfunction.
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| Academic Significance and Societal Importance of the Research Achievements |
哺乳類大脳新皮質の6層構造は脳の高次機能を担っており、その破綻は精神疾患の要因となりうるため、6層構造形成機構の解明は重要な課題であるが、いまだ明らかにされていない。本研究では、移動直後の神経細胞の挙動に着目して、Reelinを起点として神経細胞が互いに集合する分子メカニズムの一端を解明した。またReelinは複数の精神疾患の原因遺伝子として同定されており、その発症メカニズムを明らかにすることは医学的に急務である。本研究でPachygyria患者で見つかったReelin変異の機能不全のメカニズムを明らかにでき、この結果は、病因解明や他精神疾患の原因究明に繋がる可能性がある。
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