Effects of RNA modification and local translation in the growth cone on neural circuit formation

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K06464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: The University of Tokushima
• Principal Investigator: UMESHIMA Hiroki 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (40525375)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 神経発生

Outline of Final Research Achievements

Local translation of messenger RNA at the tips of neuronal processes is thought to be important for neurite outgrowth, but its regulatory mechanism remains unclear. In this study, we focused on the possibility that adenosine N6 methylation (m6A), one of the RNA chemical modifications, is involved in local translation and investigated its roles on neurite outgrowth and neuronal circuit formation by disrupting m6A-related genes using RNAi knock-down method in neurons in dissociated cultures and in the cerebral cortex. In parallel, we focused on the HSP90 gene, which is also involved in RNA granule formation, local translation and so on, and examined its roles on neuronal circuit formation.

Free Research Field

神経生物学

Academic Significance and Societal Importance of the Research Achievements

中枢神経系が適切な機能を実現するには発生過程において個々の神経細胞が適切な接続先へと神経突起を伸長させることが不可欠である。RNA修飾や局所翻訳の対象となる遺伝子には脳形成不全の一種である滑脳症の原因遺伝子として知られているものや自閉症や統合失調症などの神経疾患の関連遺伝子も多く含まれる。本研究から得られた知見から神経回路形成メカニズムへの理解がさらに発展すれば上記の神経疾患などの病態解明と治療法開発にも繋がると期待される。