Coordination of FGF and Wnt in the construction of the hierarchical branching structure of lung

• Project/Area Number: 18K06260
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Kyushu University
• Principal Investigator: Takigawa-Imamura Hisako 九州大学, 医学研究院, 助教 (30523790)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 形態形成 / 肺 / 分岐形成 / 計算機シミュレーション / 数理モデル / 発生生物学 / 血管 / 細胞運動 / 分岐 / FGF / Wnt

Outline of Final Research Achievements

The mechanism by which the pulmonary bronchi form a hierarchical structure with respect to length and diameter was investigated. Experimental results showed that the FGF signaling responsiveness of epithelium changes depending on the developmental stage, which regulates the branching frequencies, as shown by a mathematical model. I showed the importance of cell shape regulation as a modulator of branching formation when branch diameter is varied.

Academic Significance and Societal Importance of the Research Achievements

分岐理論研究の中で、本研究の特徴は、2つの異なる分岐原理を組み合わせた点にある。ひとつは上皮の突出部で成長が進むこと、もうひとつは頂端収縮を介した自発曲率変化である。本研究はFGFとWntがこれらの制御を介して分岐スケールを決定していることを示した。定量的実験に基づいた高次分岐のシミュレーションにより、上皮の性質が肺のメソスケール構造をどのように制御しているか新しい視点を提供した。

Research Products

• [Journal Article] Mesoscale regulatory mechanisms of branch formation generating hierarchical structure of the lung (2023)
  • Author(s): Hisako Takigawa-Imamura, Hiroaki Takesue, Takashi Miura
  • Journal Title: bioRxiv Volume: -
  • DOI: 10.1101/2023.03.23.533381
  • Open Access
• [Journal Article] Computational model exploring characteristic pattern regulation in periventricular vessels. (2022)
  • Author(s): Takigawa-Imamura H., Hirano S., Watanabe C., Ohtaka-Maruyama C., Ema M. & Mizutani K.
  • Journal Title: Life Volume: 12 Issue: 12 Pages: 2069-2069
  • DOI: 10.3390/life12122069
  • Peer Reviewed / Open Access
• [Journal Article] Mathematical Modeling of Dynamic Cellular Association Patterns in Seminiferous Tubules (2021)
  • Author(s): Kawamura Mari、Sugihara Kei、Takigawa-Imamura Hisako、Ogawa Toshiyuki、Miura Takashi
  • Journal Title: Bulletin of Mathematical Biology Volume: 83 Issue: 4 Pages: 33-33
  • DOI: 10.1007/s11538-021-00863-x
  • Peer Reviewed
• [Journal Article] Mechanism underlying dynamic scaling properties observed in the contour of spreading epithelial monolayer (2020)
  • Author(s): Oguma Toshiki、Takigawa-Imamura Hisako、Miura Takashi
  • Journal Title: Physical Review E Volume: 102 Issue: 6 Pages: 062408-062408
  • DOI: 10.1103/physreve.102.062408
  • Peer Reviewed / Open Access
• [Journal Article] Excess Pyrophosphate Restrains Pavement Cell Morphogenesis and Alters Organ Flatness in Arabidopsis thaliana (2020)
  • Author(s): Gunji Shizuka、Oda Yoshihisa、Takigawa-Imamura Hisako、Tsukaya Hirokazu、Ferjani Ali
  • Journal Title: Frontiers in Plant Science Volume: 11 Pages: 31-31
  • DOI: 10.3389/fpls.2020.00031
  • Peer Reviewed / Open Access
• [Journal Article] Mark1 regulates distal airspace expansion through type I pneumocyte flattening in lung development (2019)
  • Author(s): Fumoto Katsumi、Takigawa-Imamura Hisako、Sumiyama Kenta、Yoshimura Shige H.、Maehara Natsumi、Kikuchi Akira
  • Journal Title: Journal of Cell Science Volume: 132 Issue: 24
  • DOI: 10.1242/jcs.235556
  • Peer Reviewed
• [Journal Article] PtdIns (3, 5) P 2 mediates root hair shank hardening in Arabidopsis (2018)
  • Author(s): Tomoko Hirano, Hiroki Konno, Seiji Takeda, Liam Dolan, Mariko Kato, Takashi Aoyama, Takumi Higaki, Hisako Takigawa-Imamura, Masa H Sato
  • Journal Title: Nature Plants Volume: 11 Issue: 4 Pages: 447-447
  • DOI: 10.1038/s41477-019-0416-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Computational model exploring the regulation for characteristic patterns in periventricular vessels. (2022)
  • Author(s): 今村寿子, 平野才人
  • Organizer: 第45回日本分子生物学会年会
• [Presentation] Mathematical model exploring the regulation for characteristic patterns in periventricular vessels. (2022)
  • Author(s): 今村寿子, 平野才人, 水谷健一
  • Organizer: 2022年度日本数理生物学会年会
• [Presentation] 肺のヒエラルキー構造形成メカニズムの数理モデル (2021)
  • Author(s): 今村寿子
  • Organizer: 第44回日本分子生物学会年会,
  • Invited
• [Presentation] 血管内皮細胞集団による分岐構造形成のモデル化 (2021)
  • Author(s): 平野才人, 今村寿子
  • Organizer: 第31回日本数理生物学会大会
• [Presentation] 気管支の階層構造を生み出すメカニズムを実験と数理モデルから考える (2019)
  • Author(s): 今村寿子
  • Organizer: 第92回日本生化学会大会
• [Presentation] 肺の形態形成 II：細胞形状制御による組織変形の数理モデル (2019)
  • Author(s): 今村寿子、麓勝己、三浦岳
  • Organizer: 反応拡散系と実験の融合2
  • Invited
• [Presentation] FGFとWntの協同による肺分岐のヒエラルキー構造形成 (2018)
  • Author(s): 今村寿子、麓勝己、三浦岳
  • Organizer: 第15回 生物数学の理論とその応用 -次世代の数理科学への展開-への参加
  • Invited