Ca2+-dependent low-dosage Shh signaling pathway during mouse cortical development.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06674
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Doshisha University
• Principal Investigator: Motoyama Jun 同志社大学, 脳科学研究科, 教授 (70321825)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 神経幹細胞 / 細胞分化 / マウス胚 / 大脳皮質 / カルシウムイオン / Shh

Outline of Final Research Achievements

Using Ca2+ imaging, we examined temporal changes in the pattern of [Ca2+]i fluctuations during neural stem cell (NPC) development. The [Ca2+]i of undifferentiated NPCs decreased with neuronal differentiation; few undifferentiated NPCs showed transient [Ca2+]i fluctuations, but many immature neurons did; the [Ca2+]i fluctuations exhibited by NPCs were dependent on T-type calcium channels, and blocking T-type calcium channels inhibited NPC differentiation. In vivo RNAi knockdown of Cav3.1 maintained undifferentiated NPCs and inhibited neuronal differentiation. Thus, Cav3.1-mediated [Ca2+]i fluctuations are required for neuronal differentiation of undifferentiated NPCs.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では神経幹細胞の未分化状態から分化状態への変化の過程で、細胞内カルシウム濃度変動パターンが変化することを発見した。この発見は細胞が生存した状態で未分化と分化の２つの状態の違いを判別することを可能にする技術の基盤となる。幹細胞医療の実用化を進めるにあたり幹細胞の状態を非破壊で把握する技術の必要性は高い。本研究の成果はその非破壊幹細胞未分化・分化検出方法の開発の糸口になる。