| Project/Area Number |
18K14828
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Fujita Ikumi 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (80615138)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 小頭症 / Aspm / oRG / OSVZ / 細胞分裂 / 染色体分配 / 神経幹細胞 / アポトーシス / 紡錘体 / CRISPR/Cas9 / LGN / 紡錘体角度 / 接着結合 / 神経発生 / 大脳皮質 / outer radial glia / LGN/Gpsm2 / 外脳室下帯 |
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| Outline of Final Research Achievements |
In this study, we showed that the loss of the Aspm function causes chromosome mis-segregation in the developing cortex, which increases cell death and decreases brain size. Cell death by the Aspm mutation was increased by artificial induction of oRG by using the LGN mutant mice, suggesting that developing scheme with oRG is susceptible to the spindle malformation by the Aspm mutation. Increase of cell death by the oRG induction was observed during the mid and late neurogenic stages. We revealed that induction of oRG is repressed by the regeneration ability of the epithelial structure in neural stem cells during the proliferative to early neurogenic stages.
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| Academic Significance and Societal Importance of the Research Achievements |
Aspm遺伝子変異は，ヒトでは重篤な小頭症を引き起こすものの，マウスにおいてはわずかな表現型しか示さないことから，モデル動物を用いた小頭症の研究には困難が伴っていた。本研究では，LGN変異マウスを用いて人工的にoRG幹細胞を誘導することでAspm変異が重篤な小頭症を引き起こす現象を発見し，小頭症の発症機序を解明するために有用なモデル系であることを示した点で意義がある。また，oRGの発生時期特異的な誘導機構の研究を通して，神経幹細胞が発生初期には形態再生能を持つことを発見し，脳発生研究に新たな視点をもたらした。
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