Exploring extrisic mechanisms of folding formation in developing neocortex

• Project/Area Number: 18K14839
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Kumamoto University
• Principal Investigator: Sato Haruka 熊本大学, 発生医学研究所, 特定事業研究員 (70625780)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 大脳皮質 / シワ形成 / 脳回・脳溝 / 外的要因 / 発生後期 / 大脳 / 脳回 / 発生 / 外的因子 / 脳回形成

Outline of Final Research Achievements

In this study, I investigated the mechanisms of folding formation in developing neocortex. As folding becomes obvious in later developmental stage compared to neurogenesis, I focused on extrinsic factors emerged in the stage.
To study cortical folding formation, two animal species were used. One is guinea pigs, which belong to rodents, but have simple folding in the neocortex. The other is cynomolgus monkeys, which have complicated cortical folding. First, I identified for factors accumulating in gyrus during cortical folding is formed. Next, genes responsible for controlling the amount of those factors were introduced into the neocortex of guinea pig embryos. As a result, folding formation was affected by the modification of the factors. These results suggest that cortical folding formation is regulated by extrinsic factors accumulating in gyrus in later developmental stage.

Academic Significance and Societal Importance of the Research Achievements

本研究により、ニューロン以外の因子がシワ形成期に脳溝よりも脳回に多く集積することでシワ形成が誘導されることが示唆された。外的要因によるシワ形成メカニズムを示すことにより、既存の仮説とは異なる新たなシワ形成機構を明らかにすることとなり、シワ形成機構の全容解明につながると考える。

Research Products

• [Presentation] Area-specific laminar organization is regulated by thalamocortical axons through axon-derived secretory protein VGF in developing neocortex (2020)
  • Author(s): Haruka Sato, Jun Hatakeyama, Takuji Iwasato, Nobuhiko Yamamoto, Kenji Shimamura
  • Organizer: 第５３回日本発生生物学会
• [Presentation] 大脳皮質の領野特異的な層構造の形成は視床皮質軸索に由来する分泌タンパク質VGFにより制御される (2020)
  • Author(s): 佐藤晴香
  • Organizer: 第１３回神経発生討論会
• [Presentation] Area-specific laminar organization is regulated by thalamocortical axons through axon-derived NRN1 and VGF in developing neocortex (2018)
  • Author(s): Haruka Sato, Jun Hatakeyama, Takuji Iwasato, Nobuhiko Yamamoto, Kenji Shimamura
  • Organizer: ISDN 2018: 22nd Biennial Meeting of the International Society of Developmental Neuroscience
  • Int'l Joint Research
• [Remarks] 熊本大学発生医学研究所脳発生分野
  • URL: http://www.imeg.kumamoto-u.ac.jp/bunya_top/brain_morphogenesis/