Analysis of the mechanisms underlying mammalian brain development and evolution

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06253
• 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: Kyoto University
• Principal Investigator: Ohtsuka Toshiyuki 京都大学, ウイルス・再生医科学研究所, 准教授 (20324709)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 脳発生 / 脳進化 / 神経発生 / 神経幹細胞

Outline of Final Research Achievements

We observed a promoted proliferation of neural stem cells (NSCs), expansion of ventricles and the ventricular zone, marked expansion of the brain surface area, and foldings on the brain surface in the transgenic (Tg) mice in which high levels of Shh or constitutively active form of Smoothened were expressed by NSCs and neural progenitors. Furthermore, we observed that co-overexpression of Hes genes could enhance those phenotypes. In addition, we showed that the secretion of soluble factors from the choroid plexus epithelial cells (CPECs) could be achieved in the Tg mice in which choroid plexus-specific gene expression was manipulated by using the promoters of Transthyretin or F3FuguOtx2. The Tg mice showing a choroid plexus-specific Shh expression exhibited an increase in the size of choroid plexus owing to an enhanced proliferation of CPECs, in addition to a promoted proliferation of NSCs in the neocortical area.

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・前駆細胞における遺伝子発現を任意に制御可能な各種トランスジェニックマウスを作製し、大脳皮質形成への影響を解析した。Hes遺伝子による神経幹細胞の未分化性維持とShhシグナルによる細胞増殖促進効果を組み合わせることにより、大脳皮質表面積の顕著な拡大がもたらされ、哺乳動物の脳の進化（大脳新皮質の拡大＝大脳化）メカニズムの一端を担う可能性が示唆された。また、脈絡叢特異的に遺伝子発現を制御するシステムを構築し、脈絡叢から任意の液性因子の分泌が可能であること、Shhシグナルにより脈絡叢サイズの増大がもたらされることを明らかにし、脳進化過程における脈絡叢の発達の意義の一端を示した。