| Project/Area Number |
16K19689
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
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| Research Collaborator |
FUJIMORI AKIRA
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 先天異常学 / 細胞周期 / ASPM / ＡＳＰＭ |
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| Outline of Final Research Achievements |
To evaluate molecular mechanisms of ASPM in the brain, we developed conditional knock- out (cKO) mice, in which Aspm, murine orthologous gene, was lost specifically in neural stem cells. The fetal cerebral cortex showed hypoplastic at embryonic day 16 (E16) in Aspm cKO mice; however, cell proliferation and cell migration showed normal as compared with control mice. On the other hand, cell differentiation was dysregulated and an increased number of apoptosis was observed in neural stem/precursor cells in the ventricular zone as well as in young neurons in the intermediate zone and cortical plate in Aspm cKO mice brains. The results suggested that Aspm molecule might have an important role in maintenance of neural stem/precursor cells and in survival of post-mitotic neurons.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、マウス大脳皮質脳形成過程において、神経幹細胞でAspmを欠損することがアポトーシスの増加につながることを時空間的解析を駆使して明らかにした。この研究結果は、神経系発生において、Aspmが及ぼす影響を示した新たな知見であり、ASPM遺伝子が責任遺伝子であるヒト遺伝性小頭症MCPH5の発症機序の解明につながる可能性がある。また、本研究成果は、脳科学分野における基礎的知見を提供し、多くの脳形成異常・神経変性疾患の治療戦略探究への貢献が期待される。
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