Development of mRNA transportation mechanisms in neural stem/progenitor cells during evolution

• Project/Area Number: 16K20902
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology); Morphology/Structure
• Research Institution: Tohoku University
• Principal Investigator: Kikkawa Takako 東北大学, 医学系研究科, 助教 (90727851)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大脳皮質 / 放射状グリア細胞 / Cyclin D2 / mRNA輸送 / 進化 / 神経幹細胞 / CyclinD2

Outline of Final Research Achievements

During cortical development in mammals, neural stem/progenitor cells need to adequately proliferate and differentiate. Neural progenitor cells during corticogenesis are called radial glial (RG) cells because they show highly polarized morphology with long and thin processes. We have previously shown that mRNA of Cyclin D2 encoding a cell cycle regulator is transported to the basal end-foot of RG cells by the specific mRNA transportation element. We applied a CRISPR/Cas9 genome editing system in mouse embryos and selectively removed the element. We found that the mutant mice show inhibition of Cyclin D2 mRNA transportation to the basal end-foot of RG cells. These results suggest involvement of the mammalian specific cis-regulatory sequence of Cyclin D2 mRNA in the mRNA transportation to the basal end-foot of RG cells.

Research Products

• [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
• [Journal Article] Organizing activity of Fgf8 on the anterior telencephalon. (2017)
  • Author(s): Sato T, Kikkawa T, Saito T, Itoi K, Osumi N
  • Journal Title: Dev Growth Differ Volume: 59 Issue: 9 Pages: 701-712
  • DOI: 10.1111/dgd.12411
  • Peer Reviewed
• [Journal Article] Electroporation in the Rodent Embryonic Brain Using Whole Embryo Culture System. (2017)
  • Author(s): Kikkawa T, Takahashi M, Osumi N
  • Journal Title: Curr Protoc Neurosci. Volume: 78 Issue: 1 Pages: 1-16
  • DOI: 10.1002/cpns.21
  • Peer Reviewed
• [Journal Article] Gene tracing analysis reveals the contribution of neural crest-derived cells in pituitary development (2016)
  • Author(s): Ueharu H, Yoshida S, Kikkawa T, Kanno N, Higuchi M, Kato T, Osumi N, Kato Y
  • Journal Title: Journal of Anatomy Volume: 230 Issue: 3 Pages: 373-380
  • DOI: 10.1111/joa.12572
  • Peer Reviewed / Open Access
• [Journal Article] Regional volume decreases in the brain of Pax6 heterozygous mutant rats: MRI deformation-based morphometry (2016)
  • Author(s): Hiraoka, K., Sumiyoshi, A., Nonaka, H., Kikkawa, T., Kawashima, R. and Osumi, N.
  • Journal Title: PLoS One Volume: 11 Issue: 6 Pages: e0158153-e0158153
  • DOI: 10.1371/journal.pone.0158153
  • Peer Reviewed / Open Access
• [Presentation] Analyses of Cyclin D2 mRNA transportation in the cortical development using CRISPR/Cas9 genome editing system. (2017)
  • Author(s): Kikkawa, T., Inoue U, Y., Inoue, T., Osumi, N.
  • Organizer: 第10回 神経発生討論会
  • Place of Presentation: 韓国・仁川
  • Year and Date: 2017-03-10
• [Presentation] Analyses of Cyclin D2 mRNA transportation mechanism in ragial glial cells during corticogenesis using CRISPR/Cas9 genome editing system. (2017)
  • Author(s): Kikkawa, T., Inoue U, Y., Inoue, T., Osumi, N.
  • Organizer: 第40回 日本分子生物学会
• [Presentation] Analyses of Cyclin D2 mRNA transportation mechanism in neural stem/progenitor cells during cortical development. (2017)
  • Author(s): Kikkawa, T., Inoue U, Y., Inoue, T., Osumi, N.
  • Organizer: 第13回 成体脳のニューロン新生懇談会
• [Presentation] Analyses of Cyclin D2 mRNA transportation in the cortical development using CRISPR/Cas9 genome editing system. (2017)
  • Author(s): Kikkawa, T., Inoue U, Y., Inoue, T., Osumi, N.
  • Organizer: 第60回 日本神経化学会
• [Presentation] Analyses of Cyclin D2 mRNA transportation in the cortical development using CRISPR/Cas9 genome editing system. (2016)
  • Author(s): Kikkawa, T., Inoue U, Y., Inoue, T., Casingal R, C., Osumi, N.
  • Organizer: 第39回 日本分子生物学会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2016-12-01
• [Presentation] Cyclin D2 mRNA transportation in the cortical development is based on the 3’ UTR element: a CRISPR/Cas9 analysis. (2016)
  • Author(s): Kikkawa, T., Inoue U, Y., Inoue, T., Osumi, N.
  • Organizer: 第39回 日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2016-07-20