A possible mechanism for enlargement of the cortex in placental mammals by the cellular mRNA transport system

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07237
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Tohoku University
• Principal Investigator: Kikkawa Takako 東北大学, 医学系研究科, 助教 (90727851)
• Co-Investigator(Kenkyū-buntansha): 若松 義雄 東北大学, 医学系研究科, 准教授 (60311560)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 放射状グリア細胞 / 細胞周期因子 / mRNA / 進化

Outline of Final Research Achievements

The vertebrate brain is formed by the proliferation and differentiation of radial glial (RG) cells. mRNAs of CyclinD2, a cell cycle regulator, are transported to the basal end-foot of the RG cell dependent on its 3´UTR “zip code” (cis-acting transport element, CTE). We found a basal-to-apical translocation of CyclinD2 proteins along the basal processes, indicating that CyclinD2 proteins in the basal end-feet will be transported to the nuclei to modulate the cell cycle progression. In CTE deleted mice, CyclinD2 mRNA no longer localized in the basal end-feet, and the cortical thickness was reduced. Interestingly, the CTE is only conserved in placental mammals among various vertebrates. Consistently, CyclinD2 mRNAs were not detected in the basal end-feet of the opossum, a marsupial mammal, nor in chick. The basal transport of CyclinD2 mRNA in the RG cells might be involved in forming a larger cortex of placental mammals.

Free Research Field

神経発生学

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒトを含む有胎盤類の進化過程において、大脳皮質の拡大がどのようなメカニズムで起きたのかという未知の問いへアプローチすることを目的としている。本研究によって、独自に見出した神経幹細胞内CyclinD2 mRNA輸送の新たな生物学的意義を明らかにし、このユニークな機構が有胎盤類のみに存在することを発見した。本研究は、有胎盤類の脳進化メカニズムの一端を明らかにできた点で学術的意義がある。