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A possible mechanism for enlargement of the cortex in placental mammals by the cellular mRNA transport system

Research Project

Project/Area Number 20K07237
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionTohoku University

Principal Investigator

Kikkawa Takako  東北大学, 医学系研究科, 助教 (90727851)

Co-Investigator(Kenkyū-buntansha) 若松 義雄  東北大学, 医学系研究科, 准教授 (60311560)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords放射状グリア細胞 / 細胞周期因子 / mRNA / 進化 / 大脳皮質 / mRNA輸送
Outline of Research at the Start

大脳皮質の形成過程では、神経幹細胞として働く放射状グリア(RG)細胞が適切に増殖・分化し、多様なニューロンが産生される。細胞周期因子CyclinD2のmRNAはRG細胞の基底膜側突起の末端部まで輸送され、CyclinD2の3’UTR領域に輸送に必要な配列が存在する。この輸送配列は哺乳類の中でも有胎盤類にのみ保存されており、突起に輸送されるCyclinD2 が、有胎盤類の進化過程における大脳皮質の発達に貢献する可能性が考えられる。そこで本研究では、有胎盤類、有袋類および鳥類胚を用いて大脳皮質形成におけるCyclinD2 mRNAの輸送の役割を解析する。

Outline of Final Research Achievements

The vertebrate brain is formed by the proliferation and differentiation of radial glial (RG) cells. mRNAs of CyclinD2, a cell cycle regulator, are transported to the basal end-foot of the RG cell dependent on its 3´UTR “zip code” (cis-acting transport element, CTE). We found a basal-to-apical translocation of CyclinD2 proteins along the basal processes, indicating that CyclinD2 proteins in the basal end-feet will be transported to the nuclei to modulate the cell cycle progression. In CTE deleted mice, CyclinD2 mRNA no longer localized in the basal end-feet, and the cortical thickness was reduced. Interestingly, the CTE is only conserved in placental mammals among various vertebrates. Consistently, CyclinD2 mRNAs were not detected in the basal end-feet of the opossum, a marsupial mammal, nor in chick. The basal transport of CyclinD2 mRNA in the RG cells might be involved in forming a larger cortex of placental mammals.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒトを含む有胎盤類の進化過程において、大脳皮質の拡大がどのようなメカニズムで起きたのかという未知の問いへアプローチすることを目的としている。本研究によって、独自に見出した神経幹細胞内CyclinD2 mRNA輸送の新たな生物学的意義を明らかにし、このユニークな機構が有胎盤類のみに存在することを発見した。本研究は、有胎盤類の脳進化メカニズムの一端を明らかにできた点で学術的意義がある。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results)

  • [Journal Article] Deficiency of CHAMP1, a gene related to intellectual disability, causes impaired neuronal development and a mild behavioural phenotype2022

    • Author(s)
      Masayoshi Nagai, Kenji Iemura, Takako Kikkawa, Noriko Osumi, Kozo Tanaka et al.
    • Journal Title

      Brain Communications

      Volume: 4 Issue: 5

    • DOI

      10.1093/braincomms/fcac220

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thirty Years’ History since the Discovery of Pax6: From Central Nervous System Development to Neurodevelopmental Disorders2022

    • Author(s)
      Ochi Shohei、Manabe Shyu、Kikkawa Takako、Osumi Noriko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 11 Pages: 6115-6115

    • DOI

      10.3390/ijms23116115

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple Functions of the Dmrt Genes in the Development of the Central Nervous System2021

    • Author(s)
      Kikkawa Takako、Osumi Noriko
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 789583-789583

    • DOI

      10.3389/fnins.2021.789583

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex2021

    • Author(s)
      Kanlayaprasit Songphon、Thongkorn Surangrat、Panjabud Pawinee、Jindatip Depicha、Hu Valerie W.、Kikkawa Takako、Osumi Noriko、Sarachana Tewarit
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 24 Pages: 13201-13201

    • DOI

      10.3390/ijms222413201

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection of <scp>REST</scp> expression in the testis using epitope‐tag knock‐in mice generated by genome editing2021

    • Author(s)
      Kimura Ryuichi、U. Inoue Yukiko、Kikkawa Takako、Tatehana Misako、Morimoto Yuki、Inada Hitoshi、Oki Shinya、Inoue Takayoshi、Osumi Noriko
    • Journal Title

      Developmental Dynamics

      Volume: 251 Issue: 3 Pages: 525-535

    • DOI

      10.1002/dvdy.417

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sex differences in the effects of prenatal bisphenol A exposure on autism-related genes and their relationships with the hippocampus functions2021

    • Author(s)
      Thongkorn Surangrat、Kanlayaprasit Songphon、Panjabud Pawinee、Saeliw Thanit、Jantheang Thanawin、Kasitipradit Kasidit、Sarobol Suthathip、Jindatip Depicha、Hu Valerie W.、Tencomnao Tewin、Kikkawa Takako、Sato Tatsuya、Osumi Noriko、Sarachana Tewarit
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-020-80390-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Paternal age affects offspring via an epigenetic mechanism involving REST/NRSF.2021

    • Author(s)
      Yoshizaki Kaichi, Kimura Ryuichi, Kobayashi Hisato, Oki Shinya, Kikkawa Takako, Mai Lingling, Koike Kohei, Mochizumi Kentaro, Inada Hitoshi, Matsui Yasuhisa, Kono Tomohiro, Osumi Noriko
    • Journal Title

      EMBO Reports

      Volume: 22(2) Issue: 2

    • DOI

      10.15252/embr.202051524

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate Ras/MAPK, Wnt/β-catenin, and mTOR signaling during corticogenesis2020

    • Author(s)
      Casingal Cristine R.、Kikkawa Takako、Inada Hitoshi、Sasaki Yukio、Osumi Noriko
    • Journal Title

      Molecular Brain

      Volume: 13 Issue: 1 Pages: 1-13

    • DOI

      10.1186/s13041-020-00706-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic brain histamine depletion in adult mice induced depression-like behaviours and impaired sleep-wake cycle2020

    • Author(s)
      Yamada Yo、Yoshikawa Takeo、Naganuma Fumito、Kikkawa Takako、Osumi Noriko、Yanai Kazuhiko
    • Journal Title

      Neuropharmacology

      Volume: 175 Pages: 108179-108179

    • DOI

      10.1016/j.neuropharm.2020.108179

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 放射状グリア細胞内のmRNA-タンパク輸送ダイナミクスとその進化的意義2023

    • Author(s)
      吉川貴子、若松義雄、井上-上野由紀子、鈴木久仁博、井上高良、大隅典子
    • Organizer
      第128回日本解剖学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Evolution of an mRNA transport mechanism in radial glial cells by acquisition of a unique zip code sequence in placental mammals2022

    • Author(s)
      Kikkawa, T., Wakamatsu, Y., Inoue, YU., Suzuki, K., Inoue, T., Osumi, N.
    • Organizer
      第44回 日本神経科学大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Basal transport of Ccnd2 mRNA in radial glial cells is important for the production of basal progenitors in the developing mouse cortex2022

    • Author(s)
      Kikkawa, T., Wakamatsu, Y., Inoue, YU., Inoue, T., Osumi, N.
    • Organizer
      24th Biennial Meeting of the International Society for Developmental Neuroscience
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 有胎盤類特有のzip code配列獲得による放射状グリア細胞内mRNA輸送機構の進化2022

    • Author(s)
      吉川貴子、若松義雄、井上-上野由紀子、鈴木久仁博、井上高良、大隅典子
    • Organizer
      第127回日本解剖学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate mTOR signaling during corticogenesis.2021

    • Author(s)
      Kikkawa, T., Casingal, RC, Inoue, YU., Ebrahimiazar, S, Inada, H., Osumi, N.
    • Organizer
      7th Congress of AsCNP
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 放射状グリア細胞における細胞周期因子Cyclin D2のmRNA輸送機構の解析:有胎盤類の大脳皮質拡大に寄与する可能性2021

    • Author(s)
      吉川貴子、若松義雄、井上-上野由紀子、鈴木久仁博、井上高良、大隅典子
    • Organizer
      日本解剖学会 第67回東北・北海道連合支部学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Cyclin D2 mRNA and protein transport along the basal process of radial glial cells during brain development.2021

    • Author(s)
      Kikkawa, T., Wakamatsu, Y., Inoue, YU., Inoue, T., Osumi, N.
    • Organizer
      The 80th Fujiwara seminar “Molecular and cellular mechanisms of brain systems generating individuality”
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transport mechanisms of Cyclin D2 mRNA and protein along the basal process of neural stem/progenitor cells of the developing brain.2021

    • Author(s)
      Kikkawa, T., Wakamatsu, Y., Inoue, YU., Inoue, T., Osumi, N.
    • Organizer
      第44回 日本神経科学大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Analysis of mRNA transport mechanisms of a cell cycle regulator Cyclin D2 in radial glial cells: a possible mechanism of enlargement of the cortex in placental mammals.2021

    • Author(s)
      Kikkawa, T., Wakamatsu, Y. Inoue U, Kunihiro Suzuki, Inoue, T., Osumi, N.
    • Organizer
      第126回日本解剖学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Transport mechanisms of Cyclin D2 mRNA along the basal process of neural stem/progenitor cells of the developing brain.2020

    • Author(s)
      Kikkawa, T., Wakamatsu, Y. Inoue U, Inoue, T., Osumi, N.
    • Organizer
      EMBO | EMBL Symposium: The Complex Life of RNA
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 胎生期の神経前駆細胞内におけるmRNA調節メカニズム2020

    • Author(s)
      吉川貴子、Cristine Casingal、Sharmin Naher、井上-上野由紀子、井上高良、大隅典子
    • Organizer
      NPBPPP 2020合同年会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-04-28   Modified: 2024-01-30  

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