九州大学 研究者情報
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今村 寿子(いまむら ひさこ) データ更新日:2023.12.06

助教 /  医学研究院 基礎医学部門 生体制御学


主な研究テーマ
ヒト網膜黄斑部の陥凹形成の数理モデル
キーワード:網膜、黄斑、形態形成、数理モデル、計算機シミュレーション
2022.10~2024.06.
血管内皮細胞の細胞形状に依存した分岐形成の数理モデル
キーワード:数理モデル、分岐形成、血管新生、細胞形状
2020.03.
植物葉表皮細胞の変形がもたらす葉形変化の数理モデル解析
キーワード:シロイヌナズナ, Ric-1, 数理モデル, 表皮細胞
2021.01~2023.03.
細胞集団界面のフラクタル解析
キーワード:上皮細胞、細胞集団運動、自己アフィンフラクタル
2018.04~2020.12.
植物根毛の形態制御機機構の数理モデル化
キーワード:シロイヌナズナ、数理モデル、根毛
2015.10.
小腸絨毛パターン形成の座屈モデル
キーワード:小腸、絨毛、数理モデル、座屈
2015.10~2018.10.
マウス胎仔肺の分岐形成における細胞変形の役割を数理モデルを用いて考察する
キーワード:肺、形態形成、Eisukeマウス、ERK、FGF10
2015.08.
シロイヌナズナ変異株における葉表皮隆起パターンの数理モデル化
キーワード:シロイヌナズナ、数理モデル、葉表皮細胞
2015.10~2018.10.
双子葉植物の表皮細胞が示すジグソーパズルパターン形成の座屈モデル
キーワード:双子葉植物、表皮、数理モデル
2013.04~2017.05.
マウス胎仔組織と外来血管網の接続方法の確立
キーワード:組織培養、血管内皮細胞、血管、肺
2014.03~2016.06.
胎仔肺の分岐形成におけるFGFシグナルの可視化
キーワード:肺、形態形成、Eisukeマウス、ERK、FGF10
2012.04~2014.05.
マイクロ流体デバイスを用いた歯の血管形成過程の可視化
キーワード:マイクロ流体デバイス、歯胚、血管形成
2013.05~2015.05.
マイクロ流体デバイスを用いたモルフォゲン濃度勾配培養系の構築
キーワード:マイクロ流体デバイス、モルフォゲン、組織培養、形態形成
2013.03~2014.05.
血管形成過程における細胞運動をVEGFはどのように制御するか
キーワード:血管形成、細胞運動、VEGF、蛍光ラベル
2012.09~2014.05.
歯胚形態形成の数理モデル
キーワード:歯胚、数理モデル、座屈
2011.03~2013.05.
研究業績
主要原著論文
1. Hisako Takigawa-Imamura, Hiroaki Takesue, Takashi Miura, Mesoscale regulatory mechanisms of branch formation generating hierarchical structure of the lung, 10.1101/2023.03.23.533381, 2023.03, The lung airways are characterized by long and wide proximal branches and short and thin distal branches. In this study, we investigated the emergence of this hierarchical structure through experimental observations and computational models. We focused on the branch formation in the pseudoglandular stage and examined the response of mouse lung epithelium to fibroblast growth factor 10 (FGF10) by monitoring extracellular signal-regulated kinase (ERK) activity. The ERK activity increased depending on the epithelial tissue curvature. This curvature-dependent response decreased as the development progressed. Therefore, to understand how these epithelial changes affect branching morphology, we constructed a computational model of curvature-dependent epithelial growth. We demonstrated that branch length was controlled by the curvature dependence of growth that was consistent with the experimental observations and lung morphology. However, the branching of the thin branches is suppressed in this model, which is inconsistent with the fact that thin branches in the lung are short. Thus, we introduced branch formation by apical constriction, which was shown to be regulated by Wnt signaling in our previous studies. Mathematical analysis indicated that the effect of apical constriction is cell shape-dependent, suggesting that apical constriction ameliorates the branching of thin branches. Finally, we were able to provide clarity on the hierarchical branching structure through an integrated computational model of curvature-dependent growth and cell shape regulation. We proposed that curvature-dependent growth involving FGF and Wnt-mediated cell shape regulation coordinate to control the spatial scale and frequency of branch formation..
2. †Kotomi Kikukawa, †Hisako Takigawa-Imamura, Kouichi Soga, Toshihisa Kotake, Takumi Higaki, Smooth Elongation of Pavement Cells Induced by RIC1 Overexpression Leads to Marginal Protrusions of the Cotyledon in Arabidopsis thaliana, Plant And Cell Physiology, 10.1093/pcp/pcad094, 2023.09, Abstract

The interdigitated pavement cell shape is suggested to be mechanically rational at both the cellular and tissue levels, but the biological significance of the cell shape is not fully understood. In this study, we explored the potential importance of the jigsaw puzzle-like cell shape for cotyledon morphogenesis in Arabidopsis. We used a transgenic line overexpressing a Rho-like GTPase-interacting protein, ROP-INTERACTIVE CRIB MOTIF-CONTAINING PROTEIN 1 (RIC1), which causes simple elongation of pavement cells. Computer-assisted microscopic analyses, including virtual reality observation, revealed that RIC1 overexpression resulted in abnormal cotyledon shapes with marginal protrusions, suggesting that the abnormal organ shape might be explained by changes in the pavement cell shape. Microscopic, biochemical and mechanical observations indicated that the pavement cell deformation might be due to reduction in the cell wall cellulose content with alteration of cortical microtubule organization. To examine our hypothesis that simple elongation of pavement cells leads to an abnormal shape with marginal protrusion of the cotyledon, we developed a mathematical model that examines the impact of planar cell growth geometry on the morphogenesis of the organ that is an assemblage of the cells. Computer simulations supported experimental observations that elongated pavement cells resulted in an irregular cotyledon shape, suggesting that marginal protrusions were due to local growth variation possibly caused by stochastic bias in the direction of cell elongation cannot be explained only by polarity-based cell elongation, but that an organ-level regulatory mechanism is required..
3. Takigawa-Imamura H, Hirano S, Watanabe C, Ohtaka-Maruyama C, Ema M, Mizutani K., Computational model exploring characteristic pattern regulation in periventricular vessels., Life, 12, 12, 2069, 2022.12.
4. Katsumi Fumoto, Hisako Takigawa-Imamura, Kenta Sumiyama, Tomoyuki Kaneiwa, Akira Kikuchi, Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition., Development, 10.1242/dev.141325, 144, 1, 151-162, 2017.01, In lung development, the apically constricted columnar epithelium forms numerous buds during the pseudoglandular stage. Subsequently, these epithelial cells change shape into the flat or cuboidal pneumocytes that form the air sacs during the canalicular and saccular (canalicular-saccular) stages, yet the impact of cell shape on tissue morphogenesis remains unclear. Here, we show that the expression of Wnt components is decreased in the canalicular-saccular stages, and that genetically constitutive activation of Wnt signaling impairs air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage. Organ culture models also demonstrate that Wnt signaling induces apical constriction through apical actomyosin cytoskeletal organization. Mathematical modeling reveals that apical constriction induces bud formation and that loss of apical constriction is required for the formation of an air sac-like structure. We identify MAP/microtubule affinity-regulating kinase 1 (Mark1) as a downstream molecule of Wnt signaling and show that it is required for apical cytoskeletal organization and bud formation. These results suggest that Wnt signaling is required for bud formation by inducing apical constriction during the pseudoglandular stage, whereas loss of Wnt signaling is necessary for air sac formation in the canalicular-saccular stages..
5. Hisako Takigawa-Imamura, Ritsuko Morita, Takafumi Iwaki, Takashi Tsuji, Kenichi Yoshikawa, Tooth germ invagination from cell-cell interaction: Working hypothesis on mechanical instability., Journal of theoretical biology, 10.1016/j.jtbi.2015.07.006, 382, 284-91, 2015.10, In the early stage of tooth germ development, the bud of the dental epithelium is invaginated by the underlying mesenchyme, resulting in the formation of a cap-like folded shape. This bud-to-cap transition plays a critical role in determining the steric design of the tooth. The epithelial-mesenchymal interaction within a tooth germ is essential for mediating the bud-to-cap transition. Here, we present a theoretical model to describe the autonomous process of the morphological transition, in which we introduce mechanical interactions among cells. Based on our observations, we assumed that peripheral cells of the dental epithelium bound tightly to each other to form an elastic sheet, and mesenchymal cells that covered the tooth germ would restrict its growth. By considering the time-dependent growth of cells, we were able to numerically show that the epithelium within the tooth germ buckled spontaneously, which is reminiscent of the cap-stage form. The difference in growth rates between the peripheral and interior parts of the dental epithelium, together with the steric size of the tooth germ, were determining factors for the number of invaginations. Our theoretical results provide a new hypothesis to explain the histological features of the tooth germ..
主要総説, 論評, 解説, 書評, 報告書等
主要学会発表等
1. 今村寿子, Observation of FGF response in lung epithelium and modeling for
branching morphogenesis, 新学術領域研究「上皮管腔組織形成」第2回国際シンポジウム, 2015.08, The differences in cellular behavior underlying morphogenesis are governed by signaling interactions in the growing tissue. In lung branching morphogenesis, for instance, the high sensitivity of cells to the distribution of diffusive signals within the developing tissue is considered to be the principle mechanism guiding shape change. Here I investigated the response and sensitivity of lung epithelium to FGF10 that mediates epithelial branching to realize the tissue-specific shape. I demonstrated that uptake of FGF10 by epithelial explants of the pseudoglandular stage lung in Matrigel was sensitive over a wide range of FGF10 concentrations in the gel. It was also indicated that MAP kinase activity downstream of FGF10 was affected by the epithelial explant size and shape as well as the FGF10 concentration. These cellular responses of lung epithelium to FGF10 were higher in E13 than E14. To assess how these cellular responses result in shape formation of the lung epithelium, I constructed a framework employing a mathematical model in which an epithelial tip splits depending on the proliferative and chemotactic activities. Experimental results on lung epithelium were incorporated into the model and how the ordered structure of lung emerges will be discussed..
2. 今村寿子, 朽名夏麿, 桧垣匠, 秋田佳恵, 三浦 岳, 葉表皮細胞のジグソーパズル構造形成の数理モデル, 第56回日本植物生理学会年, 2015.03, シロイヌナズナの葉表皮細胞がジグソーパズル状に変形するメカニズムについて、数理モデルを用いた研究を紹介する。ここでは、細胞成長に伴いlateral側の細胞壁が伸展し座屈する(力学的に折れ曲がる)ことにより、湾曲が生じる可能性を考えた。この仮説を表現するため、細胞を質点の集合としてモデル化し、細胞壁には曲げ弾性を仮定して、張りのある構造を保つものとした。質点を増加させることで細胞成長をシミュレートしたところ、次第に細胞壁の湾曲が起こり、自発的に細胞の突出と陥入が生じることを再現できた。細胞成長の異方性を仮定した場合には、湾曲構造の振幅が小さくなり、葉柄細胞様の形状が得られた。また細胞壁の曲げ弾性を変えると、柔らかい場合には湾曲構造の波長が短くなり細胞形状が複雑化するが、極端に柔らかい場合には細胞壁が細かく縮み細胞形状が単純化することが分かった。3つの細胞が接する細胞壁の交点では、細胞壁がほぼ120度ずつ交わるが、細胞壁が極端に柔らかい場合にはこの均衡が崩れた。これらの結果は、実験的にシロイヌナズナの細胞壁を軟化処理した場合の細胞形状の特徴と一致した。さらに、細胞壁の湾曲部位には強いストレスがかかっていることもモデルから明らかとなり、ジグソーパズル状の細胞形状により力学的不均一性が生じる可能性が示唆された。.
特許出願・取得
特許出願件数  0件
特許登録件数  1件
学会活動
所属学会名
日本生物物理学会
日本分子生物学会
日本発生生物学会
日本数理生物学会
学会大会・会議・シンポジウム等における役割
2019.09.19~2019.09.19, 第92回日本生化学会大会, シンポジウム企画、座長「細胞・組織動態解析と数理モデルで解く形態形成の原理」.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2006年度~2007年度, 特別研究員奨励費, 代表, シアノバクテリアの概日リズムメカニズムを数理モデルを用いて解析する.
2009年度~2012年度, 基盤研究(B), 曲率効果に起因する心筋細胞での螺旋波形成機構.
2014年度~2015年度, 新学術領域研究, 代表, 分岐形成を生み出す細胞動態を実験-理論相互連動によって解明する.
2014年度~2016年度, 基盤研究(C), 代表, 植物表皮細胞壁のジグソーパズル構造形成メカニズム.
2018年度~2022年度, 基盤研究(C), 代表, 実験一理論相互連動による肺の階層構造形成メカニズムの解明.

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pure2017年10月2日から、「九州大学研究者情報」を補完するデータベースとして、Elsevier社の「Pure」による研究業績の公開を開始しました。