Elasticity in neuroepithelium supports cortical development

• Project/Area Number: 17K08489
• 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: Nagoya University
• Principal Investigator: Shinoda Tomoyasu 名古屋大学, 医学系研究科, 助教 (80505652)
• 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 大脳発生 / 幹細胞 / 核運動 / 神経前駆細胞 / 神経発生 / 脳発生 / 神経上皮 / 発生・分化

Outline of Final Research Achievements

Neural progenitor cells (NPCs), which are apicobasally elongated and densely packed in the developing brain, systematically move their nuclei/somata in a cell cycle-dependent manner, called interkinetic nuclear migration (IKNM). Our quantitative cell-biological and in silico analyses revealed that tissue elasticity mechanically assists an initial step of basalward IKNM. When the soma of an M-phase progenitor cell rounds up using actomyosin within the subapical space, a microzone within 10 μm from the surface, which is compressed and elastic because of the apical surface’s contractility, laterally pushes the densely neigh- boring processes of non-M-phase cells. The pressed processes then recoil centripetally and basally to propel the nuclei/somata of the progenitor’s daughter cells. Thus, indirect neighbor-assisted transfer of mechanical energy from mother to daughter helps efficient brain development.

Academic Significance and Societal Importance of the Research Achievements

「再生医療」の核となるオルガノイドの形成過程では、細胞集団が自立的に秩序立った積み重なりを産み出すことが知られていました。この「自己組織化」の原理は、実はよく判っていなかったのです。本研究で明らかになった「力の受け渡しによる細胞産生・供給方向の秩序化」は、大脳発生のみに留まらず、多細胞の積み重なりに秩序を与えて組織を形成する過程の一般的な原理のひとつであると思われます。
またヒトの脳は本研究でモデルとしたマウスよりも、はるかにたくさんの細胞が積み重なっています。もしかしたら、ヒトの脳ではより効率的で洗練された「力の受け渡し」メカニズムが存在しているのかもしれません。

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] Neural stem cells use external forces to streamline collective nuclear migration and secure cytogenesis (2018)
  • Author(s): 篠田友靖，川上巧，宮田卓樹
  • Journal Title: 生化学 Volume: 90 Issue: 6 Pages: 820-824
  • DOI: 10.14952/SEIKAGAKU.2018.900820
  • ISSN: 0037-1017
  • Year and Date: 2018-12-25
  • Peer Reviewed
• [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
• [Presentation] Elasticity in the subapical area maintains neuroepitherial structure in mammalian developing cerebral cortex (2020)
  • Author(s): Shinoda Tomoyasu, Miyata Takaki
  • Organizer: 第125回日本解剖学会・全国学術集会
  • Int'l Joint Research
• [Presentation] Novel dynamic lammelipodia-like structures in neural progenitor cells (2020)
  • Author(s): Shinoda Tomoyasu
  • Organizer: ABiS Symposium 'Forefront and future of electron microscopic imaging'
  • Int'l Joint Research
• [Presentation] 細胞間の「力」の授受が、神経系前駆細胞の秩序だった運動と大脳発生に重要である (2019)
  • Author(s): 篠田 友靖
  • Organizer: 第124回日本解剖学会総会全国学術集会
• [Presentation] Elasticity-based boosting of neuroepithelial nukleokinesis via indirect energy transfer from mother to daughter (2018)
  • Author(s): 篠田 友靖
  • Organizer: 第70回日本細胞生物学会・第51回日本発生生物学会合同大会
• [Presentation] Elasticity-based boosting of neuroepithelial nukleokinesis via indirect energy transfer from mother to daughter (2018)
  • Author(s): 篠田 友靖
  • Organizer: 第41回日本神経科学大会
• [Presentation] Elasticity-based boosting of neuroepithelial nucleokinesis via indirect energy transfer from mother to daughter. (2018)
  • Author(s): Tomoyasu Shinoda
  • Organizer: Joint annual meeting of JSDB 51st and JSCB 70th
  • Int'l Joint Research
• [Remarks] 研究トピックス
  • URL: https://www.med.nagoya-u.ac.jp/medical_J/research/pdf/PLOS_B_20180423.pdf
• [Remarks] 所属研究室HP
  • URL: https://www.takaki-miyata-lab.org/