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Regulatory mechanisms of astrocyte number and its role in cortical folding

Research Project

Project/Area Number 21K19307
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionHamamatsu University School of Medicine (2023)
Kanazawa University (2021-2022)

Principal Investigator

Shinmyo Yohei  浜松医科大学, 医学部, 教授 (00418831)

Co-Investigator(Kenkyū-buntansha) 河崎 洋志  金沢大学, 医学系, 教授 (50303904)
Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsフェレット / アストロサイト / 脳回 / 大脳 / 進化 / 大脳皮質
Outline of Research at the Start

本研究では、マウスを用いてアストロサイトの数を制御するメカニズムの解明を目指す。さらに、マウスよりも多くのアストロサイトを有するフェレットを用いることにより、進化におけるアストロサイトの数の増大を制御するメカニズムに迫る。また、我々の研究結果から、進化におけるアストロサイトの数の増大が脳回形成に重要であった可能性が示唆されている。そこで、発達した脳回を持つフェレットを用いて脳回形成におけるアストロサイトの重要性を検証する。

Outline of Final Research Achievements

While it is obvious that the number of neurons and glial cells in the cerebrum increased during mammalian evolution, it is a remarkable fact that astrocytes, a type of glial cell, increased more significantly than neurons. Therefore, it is extremely important to understand the molecular mechanism of the increase in the number of astrocytes during evolution. In this study, we have elucidated molecular mechanisms involved in the increase in the number of astrocytes. We found that regulation of proliferation by a positive-feedback loop of FGF signaling is important in determining astrocyte number in the cortex. Furthermore, we found that FGF1 expression was 10-fold higher in ferret astrocytes than in mouse astrocytes. These results suggest that differences in FGF1 expression in astrocytes may determine differences in astrocyte number among animal species.

Academic Significance and Societal Importance of the Research Achievements

皺脳動物でのアストロサイト研究の重要性は世界的に注目されていたが、その研究は遅れていた。この主たる原因は、皺脳動物の脳内のアストロサイトでの遺伝子操作が困難なためであった。重要なことに私たちは、子宮内エレクトロポレーション法、piggyBacシステム、細胞種特異的プロモーターを組みわせることにより、フェレット大脳においてアストロサイト選択的な遺伝子発現システムを確立した。その手法を用いて、アストロサイトの数の制御メカニズムの一端を明らかにした。このように、独自技術を利用して皺脳動物でのアストロサイトの解析を行った本課題は学術的に重要性の高い研究であると言える。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (14 results)

All 2024 2023 2022 2021

All Journal Article (10 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (4 results)

  • [Journal Article] Distinct subdivisions of subcortical U-fiber regions in the gyrencephalic ferret brain2024

    • Author(s)
      Yoshino Mayuko、Shiraishi Yoshitake、Saito Kengo、Kameya Narufumi、Hamabe-Horiike Toshihide、Shinmyo Yohei、Nakada Mitsutoshi、Ozaki Noriyuki、Kawasaki Hiroshi
    • Journal Title

      Neuroscience Research

      Volume: 200 Pages: 1-7

    • DOI

      10.1016/j.neures.2023.10.004

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early establishment of chloride homeostasis in CRH neurons is altered by prenatal stress leading to fetal HPA axis dysregulation2024

    • Author(s)
      Watanabe Miho、Sinha Adya Saran、Shinmyo Yohei、Fukuda Atsuo
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 17 Pages: 1373337-1373337

    • DOI

      10.3389/fnmol.2024.1373337

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Shank3a/b isoforms regulate the susceptibility to seizures and thalamocortical development in the early postnatal period of mice2023

    • Author(s)
      Okuzono Sayaka、Fujii Fumihiko、Matsushita Yuki、Setoyama Daiki、Shinmyo Yohei、Taira Ryoji、Yonemoto Kousuke、Akamine Satoshi、Motomura Yoshitomo、Sanefuji Masafumi、Sakurai Takeshi、Kawasaki Hiroshi、Han Kihoon、Kato Takahiro A.、Torisu Hiroyuki、Kang Dongchon、Nakabeppu Yusaku、Sakai Yasunari、Ohga Shouichi
    • Journal Title

      Neuroscience Research

      Volume: in press Pages: 13-19

    • DOI

      10.1016/j.neures.2023.03.001

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A New Technical Approach for Cross-species Examination of Neuronal Wiring and Adult Neuron-glia Functions2023

    • Author(s)
      Edwards-Faret Gabriela、de Vin Filip、Slezak Michal、Gollenbeck Lennart、Karaman Ruchan、Shinmyo Yohei、Batiuk Mykhailo Y.、Pando Carmen Menacho、Urschitz Johann、Rincon Melvin Y.、Moisyadi Stefan、Schnutgen Frank、Kawasaki Hiroshi、Schmucker Dietmar、Holt Matthew G.
    • Journal Title

      Neuroscience

      Volume: 508 Pages: 40-51

    • DOI

      10.1016/j.neuroscience.2022.11.029

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Isolation of ferret astrocytes reveals their morphological, transcriptional, and functional differences from mouse astrocytes2022

    • Author(s)
      Roboon Jureepon、Hattori Tsuyoshi、Nguyen Dinh Thi、Ishii Hiroshi、Takarada-Iemata Mika、Kannon Takayuki、Hosomichi Kazuyoshi、Maejima Takashi、Saito Kengo、Shinmyo Yohei、Mieda Michihiro、Tajima Atsushi、Kawasaki Hiroshi、Hori Osamu
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 16 Pages: 1-15

    • DOI

      10.3389/fncel.2022.877131

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Localized astrogenesis regulates gyrification of the cerebral cortex2022

    • Author(s)
      Shinmyo Yohei、Saito Kengo、Hamabe-Horiike Toshihide、Kameya Narufumi、Ando Akitaka、Kawasaki Kanji、Duong Tung Anh Dinh、Sakashita Masataka、Roboon Jureepon、Hattori Tsuyoshi、Kannon Takayuki、Hosomichi Kazuyoshi、Slezak Michal、Holt Matthew G.、Tajima Atsushi、Hori Osamu、Kawasaki Hiroshi
    • Journal Title

      Science Advances

      Volume: 8 Issue: 10 Pages: 1-15

    • DOI

      10.1126/sciadv.abi5209

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Investigation of the Mechanisms Underlying the Development and Evolution of the Cerebral Cortex Using Gyrencephalic Ferrets2022

    • Author(s)
      Shinmyo Yohei、Hamabe-Horiike Toshihide、Saito Kengo、Kawasaki Hiroshi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 10 Pages: 847159-847159

    • DOI

      10.3389/fcell.2022.847159

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glial cell type-specific gene expression in the mouse cerebrum using the piggyBac system and in utero electroporation2021

    • Author(s)
      Hamabe-Horiike Toshihide、Kawasaki Kanji、Sakashita Masataka、Ishizu Chihiro、Yoshizaki Tomokazu、Harada Shin-ichi、Ogawa-Ochiai Keiko、Shinmyo Yohei、Kawasaki Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 4864-4864

    • DOI

      10.1038/s41598-021-84210-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The expression of aristaless-related homeobox in neural progenitors of gyrencephalic carnivore ferrets2021

    • Author(s)
      Maeyama Hiroki、Shinmyo Yohei、Kawasaki Hiroshi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 26 Pages: 100970-100970

    • DOI

      10.1016/j.bbrep.2021.100970

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dysfunction of the proteoglycan Tsukushi causes hydrocephalus through altered neurogenesis in the subventricular zone in mice2021

    • Author(s)
      Ito Naofumi、(24/28)
    • Journal Title

      Science Translational Medicine

      Volume: 13 Issue: 587 Pages: 7896-7896

    • DOI

      10.1126/scitranslmed.aay7896

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Localized astrogenesis controls gyrification of the cerebral cortex2023

    • Author(s)
      Shinmyo Y and Kawasaki H
    • Organizer
      MBSJ2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] A positive feedback loop of FGF signaling induces astrocyte expansion and folding of the cerebral cortex in gyrencephalic animals2023

    • Author(s)
      Shinmyo Y and Kawasaki H
    • Organizer
      日本解剖学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] A positive feedback loop of FGF signaling induces astrocyte expansion and folding of the cerebral cortex in gyrencephalic animals2022

    • Author(s)
      Shinmyo Y and Kawasaki H
    • Organizer
      Development and Plasticity of the Brain
    • Related Report
      2022 Research-status Report
  • [Presentation] A positive feedback loop of FGF signaling induces astrocyte expansion and folding of the cerebral cortex in gyrencephalic animals2022

    • Author(s)
      Shinmyo Y, Saito K, Hamabe-Horiike T, Kameya N, Hattori T, Kannon T, Hosomichi K, Tajima A, Hori O and Kawasaki H
    • Organizer
      NEURO2022
    • Related Report
      2022 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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