Mechanism of RNA transport and localization in neural stem cells during corticogenesis

• Project/Area Number: 18K14999
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Tohoku University
• Principal Investigator: Kikkawa Takako 東北大学, 医学系研究科, 助教 (90727851)
• 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: ¥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)
• Keywords: mRNA輸送 / 神経幹細胞 / 細胞周期 / 大脳皮質 / 神経新生 / ｍRNAの輸送 / RNA結合タンパク質

Outline of Final Research Achievements

During corticogenesis, neural stem/progenitor cells need to adequately proliferate and differentiate to various types of neurons. Neural stem/progenitor cells in the developing cortex are called radial glial (RG) cells, as they possess highly polarized morphology with long apical/basal processes. We have previously shown in the mouse that mRNAs of CyclinD2, coding a cell cycle regulator, are transported to the basal end-foot of the RG cell. We found that the thickness of the cortex was decreased in the CyclinD2 mRNA transport element-deleted mutant mice that CyclinD2 mRNA no longer localized in the basal end-feet of RG cells, yet remained around the RG cell soma. These results suggest that CyclinD2 mRNA transport in RG cells is important to make the cortex during embryogenesis.

Academic Significance and Societal Importance of the Research Achievements

発生や細胞分化の過程では、細胞内において様々なタンパク質が時空間的に不均等に局在することにより、細胞の運命決定や特異的な機能発現に重要な役割を果たしている。神経系でこれまでに注目されていたのは、主に分化した神経細胞内のmRNA輸送・局在制御機構であった。このような研究動向の中で、本研究では、独自に見出したCyclinD2 mRNA輸送機構を起点として、これまでに考慮されてこなかった神経幹細胞内のmRNA細胞内局在制御による機能発現についてアプローチできた点で大きな意義がある。

Research Products

• [Journal Article] Dmrt genes participate in the development of Cajal-Retzius cells derived from the cortical hem in the telencephalon. (2020)
  • Author(s): Kikkawa, T., Sakayori, N., Yuuki, H., Katsuyama, Y., Matsuzaki, F., Konno, D., Abe, T., Kiyonari, H., Osumi, N.
  • Journal Title: Developmental Dynamics Volume: - Issue: 6 Pages: 698-710
  • DOI: 10.1002/dvdy.156
  • Peer Reviewed
• [Journal Article] Paternal age affects offspring’s behavior possibly via an epigenetic mechanism recruiting a transcriptional repressor REST (2019)
  • Author(s): Yoshizaki, K., Koike, T., Kimura, R., Kikkawa, T., Oki, S., Koike, K., Mochizuki, K., Inada, H., Kobayashi, H., Matsui, Y., Kono, T., Osumi, N.
  • Journal Title: bioRxiv Volume: -
  • DOI: 10.1101/550095
  • Open Access
• [Journal Article] Identification of FMRP target genes expressed in corticogenesis: implication for common phenotypes among neurodevelopmental disorders. (2019)
  • Author(s): Casingal, C, R., Kikkawa, T., Inada, H., Osumi, N.
  • Journal Title: bioRxiv Volume: -
  • DOI: 10.1101/769026
  • Open Access
• [Journal Article] Conserved and divergent functions of Pax6 underlie species-specific neurogenic patterns in the developing amniote brain (2018)
  • Author(s): Yamashita Wataru、Takahashi Masanori、Kikkawa Takako、Gotoh Hitoshi、Osumi Noriko、Ono Katsuhiko、Nomura Tadashi
  • Journal Title: Development Volume: 145 Issue: 8 Pages: 159764-159764
  • DOI: 10.1242/dev.159764
  • Peer Reviewed / Open Access
• [Journal Article] The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder (2018)
  • Author(s): Kikkawa Takako、Casingal Cristine R.、Chun Seung Hee、Shinohara Hiroshi、Hiraoka Kotaro、Osumi Noriko
  • Journal Title: Brain Research Volume: - Pages: 30111-2
  • DOI: 10.1016/j.brainres.2018.02.041
  • Peer Reviewed
• [Presentation] mRNA transport of Cyclin D2 in radial glial cells during brain development. (2020)
  • Author(s): Kikkawa, T.
  • Organizer: The 5th German-Japanize Retreat on Forebrain Development
  • Int'l Joint Research
• [Presentation] CyclinD2のmRNA輸送による有胎盤類大脳皮質の拡大機構の解明 (2020)
  • 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: 125回日本解剖学会
• [Presentation] mRNA transport mechanism of a cell cycle regulator Cyclin D2 in neural stem/progenitor cells during corticogenesis. (2019)
  • Author(s): Kikkawa, T., Wakamatsu, Y. Inoue U, Y., Tsunekawa, Y., Matsuzaki, F., Suzuki, K., Inoue, T., Osumi, N.
  • Organizer: 第42回 日本神経科学大会
• [Presentation] mRNA transport mechanism of a cell cycle regulator Cyclin D2 in neural stem/progenitor cells during corticogenesis. (2019)
  • Author(s): Kikkawa, T., Wakamatsu, Y. Inoue U, Y., Tsunekawa, Y., Matsuzaki, F., Suzuki, K., Inoue, T., Osumi, N.
  • Organizer: 20th TMIMS International Symposium “Principles of Neocortical Development and Evolution”
  • Int'l Joint Research
• [Presentation] mRNA transport mechanism of a cell cycle regulator Cyclin D2 in neural stem/progenitor cells during corticogenesis. (2019)
  • Author(s): Kikkawa, T., Wakamatsu, Y. Inoue U, Y., Tsunekawa, Y., Matsuzaki, F., Suzuki, K., Inoue, T., Osumi, N.
  • Organizer: 次世代脳プロジェクト 冬のシンポジウム2019
• [Presentation] Analyses of Cyclin D2 mRNA transport mechanism in radial glial cells during corticogenesis. (2019)
  • Author(s): Kikkawa, T., Inoue U, Y., Inoue, T., Osumi, N.
  • Organizer: 第12回 神経発生討論会
• [Presentation] Analyses of Cyclin D2 mRNA transportation mechanism in radial glial cells during corticogenesis. (2018)
  • Author(s): Kikkawa, T., Inoue U, Y., Inoue, T., Osumi, N.
  • Organizer: Special Lecture on the 5th Anniversary of the Tohoku Forum for Creativity “Genome Editing”
  • Int'l Joint Research
• [Presentation] Analyses of Cyclin D2 mRNA transportation mechanism in radial glial cells during corticogenesis. (2018)
  • Author(s): Kikkawa, T., Inoue U, Y., Inoue, T., Osumi, N.
  • Organizer: 22th Biennial Meeting of the International Society for Developmental Neuroscience
  • Int'l Joint Research
• [Presentation] Dmrt genes control the development of Cajal-Retzius cells derived from specific origins in the cerebral cortex. (2018)
  • Author(s): Kikkawa, T., Sakayori, N., Yuuki, H., Osumi, N.
  • Organizer: 第41回 日本神経科学大会