| Project/Area Number |
17K07415
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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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| Research Field |
Developmental biology
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| Research Institution | Keio University |
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Principal Investigator |
HIROTA Yuki 慶應義塾大学, 医学部(信濃町), 講師 (00453548)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 大脳皮質発生 / ニューロン移動 / リーリンシグナル / リーリン受容体 / 大脳皮質 / 受容体 |
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| Outline of Final Research Achievements |
In the developing neocortex, radially migrating neurons stop migration and form layers beneath the marginal zone (MZ). Reelin plays essential roles in these processes via its receptors, ApoER2 and VLDLR. Although we recently reported that Reelin causes neuronal aggregation via ApoER2, which is thought to be important for the subsequent layer formation, it remains unknown what effect Reelin exerts via the VLDLR. Herein, we found that ectopic Reelin overexpression in the Vldlr-mutant cortex causes neuronal aggregation, but without a MZ-like cell-sparse central region that is formed when Reelin is overexpressed in the normal cortex. We also found that both the early-born and late-born Vldlr-deficient neurons invade the MZ and exhibit impaired dendrite outgrowth from before birth. These results suggest that VLDLR is not a prerequisite for Reelin-induced neuronal aggregation and that the major role of VLDLR is to suppress neuronal invasion into the MZ during neocortical development.
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| Academic Significance and Societal Importance of the Research Achievements |
神経細胞の移動停止制御機構は、ヒト高次脳機能の獲得の仕組みの解明のため、さらに神経細胞移動の異常に起因する病態の解明のために重要な課題であるが、神経細胞移動の促進機構の研究に比較すると立ち後れているのが現状である。その理由として、一連の神経新生プロセスのうち、神経幹細胞の増殖・分化、放射状移動等の移動停止以前のステップにも機能を有する分子に着目すると、神経細胞移動停止が二次的に影響を受け解析が困難となることが挙げられる。本研究では移動停止のみが異常となるリーリン受容体VLDLRのKOマウスの解析により、大脳皮質の正常発生における神経細胞移動を制御する新規の細胞・分子メカニズムの一端を解明した。
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