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Artificial evolution from mouse cerebral cortex to primate cerebral cortex

Research Project

Project/Area Number 18K19383
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

OKADO Haruo  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 研究員 (60221842)

Project Period (FY) 2018-06-29 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsRP58 / 転写抑制因子 / OSVZ / 進化 / 大脳皮質 / 外側脳室下帯 / マウス / ROSの58 / 脳の進化 / 脳拡大 / 神経前駆細胞 / Mcl1 / 外側脳室下帯OSVZ
Outline of Final Research Achievements

In higher mammals, including primates, the number of neurons in the neocortex has increased dramatically. In mice, two proliferative layers of the neocortex have been identified, the ventricular and subventricular zones, and in higher mammals, a third proliferative layer, the lateral subventricular zone (OSVZ), has been identified. In our analysis of mice deficient in the transcriptional repressor RP58, we found OSVZ-like structures that are not found in normal mice. In order to analyze how the number of OSVZ-like structures in the mouse cerebral cortex changes as a result of the increase in the number of neurons, we attempted to increase the number of neurons in the mouse cerebral cortex in general using genetically engineered mice whose expression can be freely controlled, and to clarify whether the number of cortical neurons determines brain function.

Academic Significance and Societal Importance of the Research Achievements

マウス脳を高等ほ乳類・霊長類型脳に変容させる試みは、これまで成功していない点で、学術的に挑戦的である。細胞周期離脱を遅らせる、という方法で、実際に神経細胞の数を増加させられ、それらが、機能的に組み込まれ、個体レベルで、認知能力や、社会的機能の向上を実証することを目指し、その方法に関しては、考えられる最良な方法を試みる。マウス脳を人為的な遺伝子操作により霊長類型に変容させられれば、進化を考える上で重要な知見となり、脳研究に果たす意義は大きいと考える。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2021 2019 2018

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Open Access: 5 results,  Peer Reviewed: 7 results) Presentation (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Regulation of the cognitive aging process by the transcriptional repressor RP582021

    • Author(s)
      Tanaka Tomoko、Hirai Shinobu、Manabe Hiroyuki、Endo Kentaro、Shimbo Hiroko、Okado Haruo
    • Journal Title

      bioRxiv

      Volume: 460879 Pages: 1-40

    • DOI

      10.1101/2021.09.18.460879

    • Related Report
      2021 Annual Research Report
    • Open Access
  • [Journal Article] Early-life stress induces the development of Alzheimer's disease pathology via angiopathy2021

    • Author(s)
      Tanaka Tomoko、Hirai Shinobu、Hosokawa Masato、Saito Takashi、Sakuma Hiroshi、Saido Takaomi、Hasegawa Masato、Okado Haruo
    • Journal Title

      Experimental Neurology

      Volume: 337 Pages: 113552-113552

    • DOI

      10.1016/j.expneurol.2020.113552

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Nervous system regulated by POZ domain Kruppel-like zinc finger (POK) family transcription repressor RP582021

    • Author(s)
      Haruo Okado
    • Journal Title

      Br J Pharmacol.

      Volume: 178 Issue: 4 Pages: 813-826

    • DOI

      10.1111/bph.15265

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice2021

    • Author(s)
      Hirai Shinobu, Toriumi Kazuya (4番目/24人中), et al.
    • Journal Title

      Science Advances

      Volume: 7 Issue: 46 Pages: 1-5

    • DOI

      10.1126/sciadv.abl6077

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Corticobasal ganglia projecting neurons are required for juvenile vocal learning but not for adult vocal plasticity in songbirds2019

    • Author(s)
      Sanchez-Valpuesta M, Suzuki Y, Shibata Y, Toji N, Ji Y, Afrin N, Asogwa CN, Kojima I, Mizuguchi D, Kojima S, Okanoya K, Okado H, Kobayashi K, Wada K
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 116 Issue: 45 Pages: 22833

    • DOI

      10.1073/pnas.1913575116

    • NAID

      120006842193

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of brain development and brain function by the transcriptional repressor RP58.2019

    • Author(s)
      Okado H
    • Journal Title

      Brain Research

      Volume: 1795 Pages: 15-23

    • DOI

      10.1016/j.brainres.2018.02.042

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Zfp238 Regulates the Thermogenic Program in Cooperation with Foxo1.2019

    • Author(s)
      Kita M, Nakae J, Kawano Y, Asahara H, Takemori H, Okado H, Itoh H
    • Journal Title

      iScience

      Volume: 12 Pages: 87-101

    • DOI

      10.1016/j.isci.2019.01.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Developmental Roles and Evolutionary Significance of AMPA-Type Glutamate Receptors.2018

    • Author(s)
      Hirai S, Hotta K, Okado H.
    • Journal Title

      BioEssays

      Volume: 40 Issue: 9 Pages: 1800028-1800028

    • DOI

      10.1002/bies.201800028

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Mechanism for the maintenance of cognitive function, Neuro2019, July 25-28 Niigata2019

    • Author(s)
      Tomoko Tanaka, Okado Haruo.
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 成体でのRP58発現抑制は認知機能低下を惹起する2019

    • Author(s)
      新保 裕子, 平井 志伸, 田中 智子、田中 謙二、岡戸 晴生
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 転写抑制因子RP58の発現制御可能なトランスジェニック非ヒト動物2019

    • Inventor(s)
      岡戸晴生、新保裕子
    • Industrial Property Rights Holder
      岡戸晴生、新保裕子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report

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Published: 2018-07-25   Modified: 2023-01-30  

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