Does hereditary microcephalic responsible gene ASPM control a cell cycle and cell death in the neurogenesis process?

• Project/Area Number: 18K15683
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Tonosaki Madoka 京都府立医科大学, 医学部, 研究員 (70745637)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 先天異常学 / 細胞周期 / ASPM / アポトーシス

Outline of Final Research Achievements

To evaluate molecular mechanisms of apoptosis in the ASPM knockout brain, we developed Fucci expressing and conditional knock- out (cKO) mice, in which Aspm, murine orthologous gene, was deleted specifically in neural stem cells. As as result of timelapse imaging, apoptosis was found depending on the number of the cell cycle, however the cell cycle length was not differed. And more abnormal shaped cells were observed at the mitosis in the cKO cells. The results suggested that apoptosis in Aspm cKO cells might occur due to the disfunction related to a cell shape, not cell cycle length.

Academic Significance and Societal Importance of the Research Achievements

本研究では、Aspmの欠損によるアポトーシス発生が、細胞分裂を重ねることが関連していることを明らかにしたが、細胞増殖や細胞周期の長さなどの細胞周期制御には影響を及ぼしていないことが示唆された。この研究結果は、神経系発生において、Aspmがおよぼす影響を理解するための新たな知見であり、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への貢献が期待される。