Analysis of transcription factor Pax6 function in the dynamics of cerebrospinal fluid

• Project/Area Number: 17K08486
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Tohoku University
• Principal Investigator: Inada Hitoshi 東北大学, 医学系研究科, 講師 (60419893)
• Co-Investigator(Kenkyū-buntansha): 大隅 典子 東北大学, 医学系研究科, 教授 (00220343)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Pax6 / Sox2 / 交連下器官 / 神経幹細胞 / 上衣細胞 / 脳脊髄液 / SCO-spondin / トランスサイレチン

Outline of Final Research Achievements

Pax6 is a transcription factor essential for the development of subcommissural organ (SCO) in the brain during embryogenesis. Pax6 expression in the adult SCO was investigated and cells which consists of the SCO were characterized. Immunostaining for the several cell markers revealed that the SCO cells strongly expressed molecules of neural stem cell markers. A few BrdU labeled cells were observed. These results suggest that Pax6 expression is maintained in the adult SCO and that cells in the SCO have a feature of neural stem cells or neuroepithelial cells

Academic Significance and Societal Importance of the Research Achievements

これまでに、動物モデルにおいて交連下器官（SCO）の形成不全が水頭症様の症状を引き起こすことから、SCOの機能と水頭症発症との関連が報告されている。よって、SCOの機能がどのように維持されているか明らかにすることは、先天性水頭症の発症メカニズムを理解する上で極めて重要である。SCOの胎生期の発生に必要な転写因子Pax6が、成体のSCOにおいてもその発現が強く維持されているということは、Pax6が成体SCOの機能維持に必須であることを強く示唆している。SCOにおけるPax6の役割を理解することで、先天性水頭症の発生メカニズムに対する理解が進むと期待される。

Research Products

• [Journal Article] Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice. (2020)
  • Author(s): Misako Tatehana、 Ryuichi Kimura、 Kentaro Mochizuki、 Hitoshi Inada、 Noriko Osumi
  • Journal Title: PLOS ONE Volume: -
  • Peer Reviewed
• [Journal Article] Effects of enriched endogenous omega-3 fatty acids on age-related hearing loss in mice (2019)
  • Author(s): Honkura Yohei、Suzuki Jun、Sakayori Nobuyuki、Inada Hitoshi、Kawase Tetsuaki、Katori Yukio、Osumi Noriko
  • Journal Title: BMC Research Notes Volume: 12 Issue: 1 Pages: 768-768
  • DOI: 10.1186/s13104-019-4809-8
  • Peer Reviewed / Open Access
• [Journal Article] “Passenger gene” problem in transgenic C57BL/6 mice used in hearing research (2019)
  • Author(s): Suzuki Jun、Inada Hitoshi、Han Chul、Kim Mi-Jung、Kimura Ryuichi、Takata Yusuke、Honkura Yohei、Owada Yuji、Kawase Tetsuaki、Katori Yukio、Someya Shinichi、Osumi Noriko
  • Journal Title: Neuroscience Research Volume: - Pages: 30469-9
  • DOI: 10.1016/j.neures.2019.10.007
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structural and functional defects of the respiratory neural system in the medulla and spinal cord of Pax6 mutant rats. (2019)
  • Author(s): Ikeda Keiko, Onimaru Hiroshi, Inada Hitoshi, Tien Lin Shih, Arata Satoru, Osumi Noriko
  • Journal Title: Brain Research Bulletin Volume: 152 Pages: 107-116
  • DOI: 10.1016/j.brainresbull.2019.07.007
  • Peer Reviewed / Open Access
• [Presentation] Establishment of a high-throughput screening method to analyze proliferation of neural stem cells (2020)
  • Author(s): Inada,H., Corales,L.G., Osumi,N.
  • Organizer: 第16回 成体脳ニューロン新生懇談会・「個性」創発脳共催研究会 in 仙台2020
• [Presentation] Characterization of the subcommissural organ (SCO) in adult mouse. (2020)
  • Author(s): Corales,L.G.,Inada,H., Osumi,N.
  • Organizer: 第16回 成体脳ニューロン新生懇談会・「個性」創発脳共催研究会 in 仙台2020
• [Presentation] Pax6 expression in the subcommissural organ during brain development of juvenile mice. (2019)
  • Author(s): Inada,Hi., Hiraoka,K., Araki,S., Osumi,N.
  • Organizer: NEURO2019/第42回日本神経科学大会/第62回日本神経化学会大会
• [Presentation] Establishment of a high-throughput screening method to analyze proliferation of neural stem cells. (2019)
  • Author(s): Morisue,Y., Inada,Hi., Osumi,N.
  • Organizer: NEURO2019/第42回日本神経科学大会/第62回日本神経化学会大会
• [Presentation] Screening of functional fatty acids affecting proliferation of the mouse cultured astrocytes. (2019)
  • Author(s): Inada,H., Corales,L.G., Osumi,N.
  • Organizer: 第6回アジア神経精神薬理学会(AsCNP2019)/第49回日本神経精神薬理学会（JSNP2019）/第29回日本臨床精神神経薬理学会（JSCNP2019）
• [Presentation] Effect of fatty acids on mitochondrial activity of the mouse cultured astrocytes. (2019)
  • Author(s): Inada,H., Corales,L.G., Osumi,N.
  • Organizer: 第42回日本分子生物学会年会
  • Int'l Joint Research
• [Presentation] 細胞特異的Pax6欠損マウス(GFAP-cre;Pax6-floxマウス)における表現型の解析 (2018)
  • Author(s): 稲田仁、荒木峻、山中慎也、大隅典子
  • Organizer: 次世代脳プロジェクト冬のシンポジウム2018
• [Presentation] Pax6 is expressed in the choroid plexus and subcommissural organ (SCO) during brain development of juvenile mouse. (2017)
  • Author(s): Shun Araki, Shinya Yamanaka, Hitoshi Inada, and Noriko Osumi
  • Organizer: Annual meeting of SfN, Neuroscience 2017