Analysis of MCPH genes in mice with induced outer radial glia

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14828
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Institute of Physical and Chemical Research
• 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)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 小頭症 / Aspm / oRG / OSVZ / 細胞分裂 / 染色体分配

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.

Free Research Field

発生生物学

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。