Artificial evolution from mouse cerebral cortex to primate cerebral cortex

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K19383
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: OKADO Haruo 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 研究員 (60221842)
• Project Period (FY): 2018-06-29 – 2022-03-31
• Keywords: RP58 / 転写抑制因子 / OSVZ / 進化 / 大脳皮質

Outline of Final Research Achievements

In higher mammals, including primates, the number of neurons in the neocortex has increased dramatically. In mice, two proliferative layers of the neocortex have been identified, the ventricular and subventricular zones, and in higher mammals, a third proliferative layer, the lateral subventricular zone (OSVZ), has been identified. In our analysis of mice deficient in the transcriptional repressor RP58, we found OSVZ-like structures that are not found in normal mice. In order to analyze how the number of OSVZ-like structures in the mouse cerebral cortex changes as a result of the increase in the number of neurons, we attempted to increase the number of neurons in the mouse cerebral cortex in general using genetically engineered mice whose expression can be freely controlled, and to clarify whether the number of cortical neurons determines brain function.

Free Research Field

脳発達

Academic Significance and Societal Importance of the Research Achievements

マウス脳を高等ほ乳類・霊長類型脳に変容させる試みは、これまで成功していない点で、学術的に挑戦的である。細胞周期離脱を遅らせる、という方法で、実際に神経細胞の数を増加させられ、それらが、機能的に組み込まれ、個体レベルで、認知能力や、社会的機能の向上を実証することを目指し、その方法に関しては、考えられる最良な方法を試みる。マウス脳を人為的な遺伝子操作により霊長類型に変容させられれば、進化を考える上で重要な知見となり、脳研究に果たす意義は大きいと考える。