Tubular tissue mechanics modulated by patterned actin cytoskeleton

• Project/Area Number: 18K14746
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44040:Morphology and anatomical structure-related
• Research Institution: Tohoku University (2020-2021); Institute of Physical and Chemical Research (2018-2019)
• Principal Investigator: Sekine Sayaka 東北大学, 生命科学研究科, 助教 (00794398)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アクチン / 管構造 / 超解像顕微鏡 / ショウジョウバエ / 粗視化分子動力学モデル / 管状組織 / ナノクラスター / 自己組織化 / 等間隔アクチンリング / 管状上皮 / 筋原繊維 / Z-disc / 上皮細胞 / 張力

Outline of Final Research Achievements

Here we show the periodic circumferential actin cables were originated from the actomyosin nanoclusters at apical cortex of the tracheal epithelial cells. During expansion of the tracheal tube, the nanoclusters showed dynamic circumferential motility and biased-fusion that leaded to the directional cable formation. The clustering of actin filaments were dependent on crosslinkers, whereas sensing of the tubular axis were strongly dependent on the formin family protein. Based on our computational simulations with feasible parameters, the regularly-spaced clusters were self-organized by the interplay of actin filaments and crosslinkers, which also ruled the size and distance between the clusters. Altogether, we propose the self-organized actin nanoclusters as functional units which are sensitive for tubular axis, thus enables the periodic circumferential patterning in the tubular development.

Academic Significance and Societal Importance of the Research Achievements

血管や消化管など生体内で広く見られる管構造は、物質を効率的に運ぶのに有利だが、一方で拡張やねじれに耐える柔軟かつ強靭な細胞骨格が必要とされる。本研究は、その一つとして等間隔アクチンリングという骨格パターンが採用されていると考え、その形成機構を明らかにした。この成果により、管構造不全の治療への応用、そして人工管組織構築の改善が期待される。
また、生体内でのアクチンパターンの形成過程をここまで詳細に解析した例は少なく、これまで培養細胞での観察に留まっていた微小集合体を生体内で再発見するとともに、その挙動が組織形成に強く関わるという生物学的意義を見出したということで学術的な意義も大きい。

Research Products

• [Journal Article] Nanopore Formation in the Cuticle of an Insect Olfactory Sensillum (2019)
  • Author(s): Toshiya Ando, Sayaka Sekine, Sachi Inagaki, Kazuyo Misaki , Laurent Badel, Hiroyuki Moriya, Mustafa M. Sami, Yuki Itakura, Takahiro Chihara, Hokto Kazama , Shigenobu Yonemura, Shigeo Hayashi
  • Journal Title: Current Biology Volume: 29 Issue: 9 Pages: 1512-1520
  • DOI: 10.1016/j.cub.2019.03.043
  • Peer Reviewed
• [Presentation] Microphase separation of actomyosin during tracheal development in Drosophila embryo (2022)
  • Author(s): Mitsusuke Tarama, Sayaka Sekine, Tatsuo Shibata, Shigeo Hayashi
  • Organizer: 物理学会第77回年次大会
• [Presentation] Emergence of circumferential actin cables from clustered cross linked actin filaments during tubulogenesis (2021)
  • Author(s): Sayaka Sekine, Mustafa M. Sami, Housei Wada and Shigeo Hayashi
  • Organizer: Annual meeting of Japanese society of developmental biology 2021
• [Presentation] Emergence of circumferential actin cables from clustered cross linked actin filaments during tubulogenesis (2021)
  • Author(s): Sayaka Sekine, Mustafa M. Sami and Shigeo Hayashi
  • Organizer: 14th Japan Drosophila Research Conference
• [Presentation] The rapid biased-disconnection of discrete actomyosin clusters form circumferential actin cable in the tubular tissue (2020)
  • Author(s): Sayaka Sekine, Housei Wada, Mustafa Sami, Shigeo Hayashi
  • Organizer: 第43回日本分子生物学会年会
• [Presentation] Super-resolution live imaging of supercellular circumferential actin cable formation during tracheal tubulogenesis (2018)
  • Author(s): Sayaka Sekine
  • 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