Roles for the pace control of neurogenesis in brain histogenesis

• Project/Area Number: 16K07375
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Kumamoto University
• Principal Investigator: Shimamura Kenji 熊本大学, 発生医学研究所, 教授 (70301140)
• Co-Investigator(Kenkyū-buntansha): 畠山 淳 熊本大学, 発生医学研究所, 助教 (90404350)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経発生 / 組織構築 / 神経幹細胞 / 神経分化 / ニューロン / 脳発生 / 大脳皮質 / 皮質 / 神経核 / 分化制御 / 脳 / 接着帯 / 領域性 / 神経分化制御 / 脳組織構築 / 領域化

Outline of Final Research Achievements

We found that the transient retention of the apical endfoot of differentiating cells regulates the pace of neuron production through Notch signaling. We extend this notion to explore its role in brain histogenesis. We found that the retention period is correlated with the pace of neuron production in developing cerebral cortex and that the proper time length of retention is crucial for formation of well-proportioned six-layered structure of cerebral cortex. These results were published in Cerebral Cortex.

Academic Significance and Societal Importance of the Research Achievements

ニューロン産生量の時間的調節機構について、およびそれが大脳皮質織構築にはたす役割について初めて明らかにした。皮質構築異常は、多くの先天性脳疾患、精神疾患等で報告されており、これらの疾患の病因・病態解明、治療法の開発に寄与する可能性がある。

Research Products

• [Int'l Joint Research] Korea Brain Research Institute(韓国)
• [Int'l Joint Research] Korea Brain Research Institute(韓国)
• [Int'l Joint Research] KAIST(韓国)
• [Int'l Joint Research] Korea Brain Research Institute(韓国)
• [Journal Article] Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice. (2019)
  • Author(s): Acebedo AR, Suzuki K, Hino S, Alcantara MC, Sato Y, Haga H, Matsumoto KI, Nakao M, Shimamura K, Takeo T, Nakagata N, Miyagawa S, Nishinakamura R, Adelstein RS, Yamada G.
  • Journal Title: Commun. Biol. Volume: eCollection Issue: 1 Pages: 95-95
  • DOI: 10.1038/s42003-019-0336-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Pace of Neurogenesis Is Regulated by the Transient Retention of the Apical Endfeet of Differentiating Cells (2018)
  • Author(s): Hatakeyama Jun、Shimamura Kenji
  • Journal Title: Cerebral Cortex Volume: 印刷中 Issue: 9 Pages: 3725-3737
  • DOI: 10.1093/cercor/bhy252
  • Peer Reviewed
• [Journal Article] Developing guinea pig brain as a model for cortical folding (2017)
  • Author(s): Hatakeyama Jun、Sato Haruka、Shimamura Kenji
  • Journal Title: Development, Growth & Differentiation Volume: 59 Issue: 4 Pages: 286-301
  • DOI: 10.1111/dgd.12371
  • Peer Reviewed
• [Journal Article] Roles of CD34+ cells and ALK5 signaling in the reconstruction of seminiferous tubule-like structures in 3-D re-aggregate culture of dissociated cells from neonatal mouse testes (2017)
  • Author(s): Abe Shin-ichi、Abe Kazuko、Zhang Jidong、Harada Tomoaki、Mizumoto Go、Oshikawa Hiroki、Akiyama Haruhiko、Shimamura Kenji
  • Journal Title: PLOS ONE Volume: 12 Issue: 11 Pages: e0188705-e0188705
  • DOI: 10.1371/journal.pone.0188705
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The retinal pigment epithelium is a Notch signaling niche in the mouse retina (2017)
  • Author(s): Ha, T., Moon, K.H., Dai, L., Hatakeyama, J., Yoon, K., Park, H-S., Kong, Y-Y., Shimamura, K., Kim, J.W
  • Journal Title: Cell Rep. Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Developing guinea pig brain as a model for cortical folding. (2017)
  • Author(s): Hatakeyama, J., Sato, H., Shimamura, K.
  • Journal Title: Dev. Growth. Differ. Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Novel intrinsic and extrinsic mechanisms for the proper laminar organization of the cerebral cortex (2019)
  • Author(s): Shimamura K.
  • Organizer: Kumamoto-NCBS/Instem Partnership Meeting
• [Presentation] Area-specific laminar organization is regulated by thalamocortical axonz through axon-derived NRN1 and VGF in developing neocortex (2018)
  • Author(s): Sato H, Hatakeyama J, Iwasato T, Yamamoto N, Shimamura K.
  • Organizer: The 22nd Biennial Meeting of the International Society for Developmental Neuroscience
  • Int'l Joint Research
• [Presentation] Novel rolesof Fgf signaling in the development of chick hindbrain. (2018)
  • Author(s): Hatakeyama j, Shimamura K.
  • Organizer: The 22nd Biennial Meeting of the International Society for Developmental Neuroscience
  • Int'l Joint Research
• [Presentation] Thalamocortical axons regulate area-specific laminat configuration via secreting factor VGF (2018)
  • Author(s): Shimamura K.
  • Organizer: NIG Symposiumn "Circuit construction in the mammalian brain"
  • Invited
• [Presentation] A role for the choroid plexus in the cortical expansion in primates (2017)
  • Author(s): Shimamura, K., Hatakeyama, J., Sato, H., Matsushita, R., Tsuchiya, H., Sasaki, K., Saitou, M., Isomura, A., Shimojo, H., Kageyama, R.
  • Organizer: CBD Symposium
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2017-03-27
  • Int'l Joint Research
• [Presentation] Extrinsic factors and the cortical expansion in primates (2017)
  • Author(s): 畠山淳、嶋村健児
  • Organizer: 日本神経科学会
  • Invited
• [Presentation] The role of thalamic afferents in the formation of the area-specific laminar configuration in the developing neocortex (2017)
  • Author(s): 佐藤晴香、畠山淳、岩里琢冶、山本宣彦、嶋村健児
  • Organizer: 日本神経科学会
• [Presentation] Roles of extrinsic factors in the cortical expansion in pirimates (2017)
  • Author(s): 畠山淳、佐藤晴香、松下理香、土屋英明、斎藤通紀、影山龍一郎、嶋村健児
  • Organizer: 日本発生生物学会
  • Invited
• [Presentation] 霊長類の脳はいかにして大きくなったのか？ (2016)
  • Author(s): 畠山淳、佐藤晴香、松下理香、影山龍一郎、斎藤通紀、土屋英明、嶋村健児
  • Organizer: 日本進化学会第18回大会
  • Place of Presentation: 東京都目黒区
  • Year and Date: 2016-08-25
  • Invited