Live imaging and molecular mechanism analysis of mouse embryonic brain development

• Project/Area Number: 17K10176
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Nagoya University
• Principal Investigator: saito kanako 名古屋大学, 医学系研究科, 特任助教 (50746906)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 大脳発生 / ライブ観察 / ニューロン移動 / 子宮内ライブ観察 / 胎児医学 / 脳神経発生

Outline of Final Research Achievements

This study, we elucidated that how the embryonic pallium expands ventrally to form the future cortex and the nature of the underlying force-generating events. We find that neurons born at embryonic day 10 (E10) in the mouse dorsal pallium ventrally stream, thereby superficially spreading the preplate, and then constitute the subplate. The preplate neurons migrate, exerting pulling and pushing forces at the process and the soma, respectively. Ablation of these E10-born neurons attenuates both deflection of radial glial fibers and extension of the cortical plate, which should occur ventrally, and subsequently shrinks the postnatal neocortical map dorsally. Thus, the preplate stream physically primes neocortical expansion and arealization.

Academic Significance and Societal Importance of the Research Achievements

本研究は、ヒトの先天性脳疾患の病態解明、および将来的な臨床診断ないし胎児治療の基盤となる知見を得るため、新規なライブ観察・解析の方法を確立するとともに、マウス大脳発生過程において研究代表者らが新たに見いだしたニューロン動態(接線方向移動)をリアルタイムに捉え、ニューロン移動の分子機構や意義を解明することで、胎児医学・先天異常学に新しい方法論と視点を提供できると期待される。

Research Products

• [Journal Article] Two-photon microscopic observation of cell-production dynamics in the developing mammalian neocortex in utero (2020)
  • Author(s): Kawasoe, R, Shinoda, T, Hattori, Y, Nakagawam M, Quang Pham, T, Tanaka, Y, Sagou, K, Saito, K, Katsuki, S, Kotani, T, Sano, A, Fujimori, T, Miyata, T.
  • Journal Title: Development, Growth & Differentiation Volume: 62 Issue: 2 Pages: 118-128
  • DOI: 10.1111/dgd.12648
  • Peer Reviewed / Open Access
• [Journal Article] Dorsal-to-Ventral Cortical Expansion Is Physically Primed by Ventral Streaming of Early Embryonic Preplate Neurons (2019)
  • Author(s): Saito Kanako、Okamoto Mayumi、Watanabe Yuto、Noguchi Namiko、Nagasaka Arata、Nishina Yuta、Shinoda Tomoyasu、Sakakibara Akira、Miyata Takaki
  • Journal Title: Cell Reports Volume: 29 Issue: 6 Pages: 1555-1567
  • DOI: 10.1016/j.celrep.2019.09.075
  • Peer Reviewed / Open Access
• [Journal Article] Lzts1 controls both neuronal delamination and outer radial glial-like cell generation during mammalian cerebral development (2019)
  • Author(s): Kawaue T.、Shitamukai A.、Nagasaka A.、Tsunekawa Y.、Shinoda T.、Saito K.、Terada R.、Bilgic M.、Miyata T.、Matsuzaki F.、Kawaguchi A.
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 2780-2780
  • DOI: 10.1038/s41467-019-10730-y
  • NAID: 120006649601
  • Peer Reviewed / Open Access
• [Journal Article] Elasticity-based boosting of neuroepithelial nukleokinesis via indirect energy transfer from mother to daughter (2018)
  • Author(s): Tomoyasu Shinoda, Arata Nagasaka, Yasuhiro Inoue, Ryo Higuchi, Yoshiaki Minami, Kagayaki Kato, Makoto Suzuki, Takefumi Kondo, Takumi Kawaue, Kanako Saito, Naoto Ueno, Yugo Fukazaawa, Masaharu Nagayama, Takashi Miura, Taiji Adachi, Takaki Miyata
  • Journal Title: PLoS Biology Volume: 16 Issue: 4 Pages: 2004426-2004426
  • DOI: 10.1371/journal.pbio.2004426
  • Peer Reviewed / Open Access
• [Journal Article] Neural progenitor cells undergoing Yap/Tead-mediated enhanced self-renewal form heterotopias more easily in the diencephalon than in the telencephalon. (2018)
  • Author(s): K.Saito, R. Kawasoe, H. Sasaki, A. Kawaguchi and T. Miyata
  • Journal Title: Neurochem Res Volume: 43 Issue: 1 Pages: 171-180
  • DOI: 10.1007/s11064-017-2390-x
  • Peer Reviewed / Open Access
• [Presentation] Dorsal-to-Ventral neocortical expansion is physically primed by ventral streaming of early embryonic prelate neurons. (2019)
  • Author(s): Saito Kanako、Okamoto Mayumi、Watanabe Yuto、Nagasaka Arata、Miyata Takaki
  • Organizer: 第５２回発生生物学会合同大会
• [Presentation] Dorsal-to-Ventral neocortical expansion is physically primed by ventral streaming of early embryonic prelate neurons. (2019)
  • Author(s): Saito Kanako、Okamoto Mayumi、Watanabe Yuto、Nagasaka Arata、Miyata Takaki
  • Organizer: 第４２回日本神経科学学会
• [Presentation] 大脳新皮質の腹側方向への拡張的形成には胎生初期プレプレートニューロンの腹側移動が物理的に貢献する (2019)
  • Author(s): 齋藤加奈子、岡本麻友美、渡邊裕斗、宮田卓樹
  • Organizer: 第124回日本解剖学会総会・全国学術集会
• [Presentation] Dorsal-to-ventral neocortical expansion is physically primed by ventral streaming of early embryonic preplate neurons (2019)
  • Author(s): kanako saito, tomomi okamoto, yuto watanabe, arata nagasaka, takaki miyata
  • Organizer: 第52回発生生物学会合同大会
• [Presentation] The preplate stream: neurons generated earliest in the pallium migrate ventrally to mechanically bend radial fibers and expand the neocortex (2018)
  • Author(s): kanako saito, takaki miyata
  • Organizer: 第70回細胞生物学会・第51回発生生物学会合同大会
• [Presentation] Novel tangential (ventral) migration of the early pallium-derived neurons underlies the neocortical expansion (2017)
  • Author(s): Saito Kanako、Miyata Takaki
  • Organizer: 第40回日本神経科学大会