The role of forces and the cellular responses to them as a mechanism for epithelial morphogenesis

• Project Area: Cross-talk between moving cells and microenvironment as a basis of emerging order in multicellular systems
• Project/Area Number: 22111007
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Hayashi Shigeo 国立研究開発法人理化学研究所, 多細胞システム形成研究センター, チームリーダー (60183092)
• Co-Investigator(Renkei-kenkyūsha): HONDA HISAO 神戸大学, 医学研究科, 研究員 (10289118)
• Project Period (FY): 2010-04-01 – 2016-03-31
• Project Status: Completed(Fiscal Year 2015)
• Budget Amount: ¥51,740,000 (Direct Cost : ¥39,800,000、Indirect Cost : ¥11,940,000); Fiscal Year 2014 : ¥9,620,000 (Direct Cost : ¥7,400,000、Indirect Cost : ¥2,220,000); Fiscal Year 2013 : ¥10,140,000 (Direct Cost : ¥7,800,000、Indirect Cost : ¥2,340,000); Fiscal Year 2012 : ¥10,660,000 (Direct Cost : ¥8,200,000、Indirect Cost : ¥2,460,000); Fiscal Year 2011 : ¥10,530,000 (Direct Cost : ¥8,100,000、Indirect Cost : ¥2,430,000); Fiscal Year 2010 : ¥10,790,000 (Direct Cost : ¥8,300,000、Indirect Cost : ¥2,490,000)
• Keywords: 細胞生物学 / 形態形成 / 上皮 / イメージング / 力学 / 遺伝学 / ショウジョウバエ / 細胞外基質 / 管腔形成 / 陥入 / Drosophila / 気管 / 細胞分裂 / 定量生物学 / 細胞運動 / 細胞骨格 / ライブイメージング / シミュレーション

Outline of Final Research Achievements

We studied the mechanical basis of epithelial movement and its interaction with extracellular environment. Our main research focus is the tracheal system in the Drosophila embryo, a network of tubular epithelium used as a respiratory organ. Epithelium is stabilized by cell-cell adhesion and cell-matrix adhesion. Breaking this stability is essential for initiating morphogenetic movement. We found that prospective tracheal primordium is under negative tension (pressurized). Anisotropic redistribution of tissue tension and timely mitosis initiates local mechanical instability that leads to tissue invagination movement. We also studied the tube lumen size control and found that extracellular matrix in the luminal space coordinates random movement of individual tubule cells to form coherent tissue architecture.

Research Products

• [Int'l Joint Research] キュリー研究所(フランス)
• [Int'l Joint Research] ベングリオン大学(イスラエル)
• [Int'l Joint Research] 青島海洋大学(中国)
• [Journal Article] Microtubule-dependent balanced cell contraction and luminal-matrix modification accelerate epithelial tube fusion. (2016)
  • Author(s): Kato, K., Dong, B., Wada, H., Tanaka-Matakatsu, M., Yagi, Y., Hayashi, S.
  • Journal Title: Nature Communications Volume : 7 Pages : 000-000
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A cortical instability drives periodic supracellular actin pattern formation in epithelial tubes. (2015)
  • Author(s): Hanezzo E., Dong B., Recho P., Joanny J-F., Hayashi S.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume : 112 Pages : 8211-8625
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Transport and retention mechanism for the sustained distal localization of Spn-F/ IKKε during Drosophila bristle elongation. (2015)
  • Author(s): Otani T., Oshima K., Kimpara A., Takeda M., Abdu U., Hayashi S.
  • Journal Title: Development Volume : 142 Pages : 2338-2351
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Shaping of biological tubes by mechanical interaction of cell and extracellular matrix. (2015)
  • Author(s): Dong B., Hayashi S.
  • Journal Title: Current Opinion in Genetics & Development Volume : 32 Pages : 129-134
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mechanisms of cell height changes that mediate epithelial invagination. (2015)
  • Author(s): Kondo T., Hayashi S.
  • Journal Title: Develp. Growth and Diff. Volume : 57 Pages : 313-323
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TALEN-induced gene knock out in Drosophila. (2014)
  • Author(s): Kondo T
  • Journal Title: Development Growth and Differentiation Volume : 56:1 Pages : 86-91
  • Peer Reviewed
• [Journal Article] Balance between Apical Membrane Growth and Luminal Matrix Resistance Determines Epithelial Tubule Shape. (2014)
  • Author(s): Dong B, Hannezo E, Hayashi S
  • Journal Title: Cell Reports Volume : (14)00263-0 Pages : 1-10
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Efficient TALEN construction and evaluation methods for human cell and animal applications (2013)
  • Author(s): Sakuma T
  • Journal Title: Genes Cells Volume : 18:4 Pages : 315-326
  • Peer Reviewed
• [Journal Article] Homeogenetic inductive mechanism of segmentation in polychaete tail regeneration. (2013)
  • Author(s): Niwa N
  • Journal Title: Developmental Biology Volume : 381: 2 Pages : 460-470
  • Peer Reviewed
• [Journal Article] TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding. (2013)
  • Author(s): Okamoto M, Namba T, Shinoda T, Kondo T, Watanabe T, Inoue Y, Takeuchi K, Enomoto Y, Ota K, Oda K, Wada Y, Sagou K, Saito K, Sakakibara A, Kawaguchi A, Nakajima K, Adachi T, Fujimori T, Ueda M, Hayashi S, Kaibuchi K, Miyata T
  • Journal Title: Nature Neuroscience Volume : 16 Pages : 1556-66
  • Peer Reviewed / Open Access
• [Journal Article] Drosophila oocyte polarity and cytoskeleton organization requires regulation of Ik2 activity by Spn-F and Javelin-like. (2013)
  • Author(s): Amsalem S
  • Journal Title: Molecular and Cellular Biology Volume : 33:22 Pages : 4371-4380
  • Peer Reviewed
• [Journal Article] Sustained elongation of sperm tail promoted by local remodeling of giant mitochondria in Drosophila (2011)
  • Author(s): Noguchi T, Koizumi M, Hayashi S
  • Journal Title: Curr Biol Volume : 21 Pages : 805-814
  • Peer Reviewed
• [Journal Article] Joint morphology in the insect leg : evolutionary history inferred from Notch loss-of-function phenotypes in Drosophila (2011)
  • Author(s): Tajiri R, Misaki K, Yonemura S, Hayashi S
  • Journal Title: Development Volume : 138 Pages : 4621-4626
  • Peer Reviewed
• [Journal Article] Robust specification of sensory neurons by dual functions of charlatan, a Drosophila NRSF/REST-like repressor of extramacrochaetae and hairy (2011)
  • Author(s): Yamasaki Y
  • Journal Title: Genes Cells Volume : 16 Pages : 896-909
  • Peer Reviewed
• [Journal Article] IKKε regulates cell elongation through recycling endosome shuttling (2011)
  • Author(s): Tetsuhisa Otani
  • Journal Title: Developmental Cell Volume : 20 Pages : 219-232
  • Peer Reviewed
• [Journal Article] Evolutionary origin of the insect wing via integration of two developmental modules. (2010)
  • Author(s): Nao Niwa
  • Journal Title: Evolution & Development Volume : 12 Pages : 168-176
  • Peer Reviewed
• [Journal Article] Dynamic intracellular distribution of Notch during activation and asymmetric cell division revealed by functional fluorescent fusion proteins. (2010)
  • Author(s): Koji Kawahashi
  • Journal Title: Genes to Cells Volume : 15 Pages : 749-759
  • Peer Reviewed
• [Journal Article] Dynamic shape changes of ECM-producing cells drive morphogenesis of ball-and-socket joints in the fly leg. (2010)
  • Author(s): Reiko Tajiri
  • Journal Title: Development Volume : 137 Pages : 2055-2063
  • Peer Reviewed
• [Presentation] Genetic and physical mechanisms behind tube geometry and size control (2016)
  • Author(s): 林 茂生
  • Organizer: CDB Symposium 2016 “Size in Development: Growth, Shape and Allometry”
  • Place of Presentation: 理化学研究所、兵庫県、神戸市
  • Year and Date: 2016-3-28
  • Int'l Joint Research / Invited
• [Presentation] Transport and retention mechanism for the sustained distal organizer localization during Drosophila bristle elongateion (2015)
  • Author(s): 林 茂生
  • Organizer: Asian-Pacific Developmental Biology Conference,
  • Place of Presentation: Xian China
  • Year and Date: 2015-9-12
  • Int'l Joint Research / Invited
• [Presentation] Cell extrusion from epithelia undergoing morphogenetic movement (2015)
  • Author(s): 林 茂生
  • Organizer: 1st International Symposium on Cell Competition, “Cell Competition in Development and Cancer”
  • Place of Presentation: 芝蘭会館、京都府、京都市
  • Year and Date: 2015-9-10
  • Int'l Joint Research / Invited
• [Presentation] Role of apical extracellular matrix in epithelial tube morphogenesis (2015)
  • Author(s): 林 茂生
  • Organizer: Asian-Pacific Drosophila Conference,
  • Place of Presentation: Beijin, China
  • Year and Date: 2015-5-13
  • Int'l Joint Research / Invited
• [Presentation] ショウジョウバエ気管原基における陥入過程の形態学的定量解析 (2014)
  • Author(s): Hayashi S
  • Organizer: 動く細胞と場のクロストークによる秩序の生成, 第八回領域班会議
  • Place of Presentation: 横浜市
• [Presentation] The role of mitotic cell rounding and mechanical instability in epithelial morphogenesis (2013)
  • Author(s): Hayashi S
  • Organizer: The 2nd Asia-Pacific Drosophila Research Conference
  • Place of Presentation: ソウル、韓国
• [Presentation] A self-sustaining signaling center controls cell elongation (2013)
  • Author(s): Otani T
  • Organizer: The 2nd Asia-Pacific Drosophila Research Conference
  • Place of Presentation: ソウル、韓国
• [Presentation] Mechanical coupling of apical membrane and luminal matrix shapes tracheal tube geometry in Drosophila (2013)
  • Author(s): Dong B
  • Organizer: 第46回日本発生生物学会大会
  • Place of Presentation: 松江市
• [Presentation] IKKe antagonizes PKC-dependent inhibitory phosphorylation of Singed/Fascin to promote (2013)
  • Author(s): Otani T
  • Organizer: 第46回日本発生生物学会大会
  • Place of Presentation: 松江市
• [Presentation] A self-sustaining signaling center controls cell elongation (2013)
  • Author(s): Otani T
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: 名古屋市
• [Presentation] Mitotic cell rounding accelerates invagination of the Drosophila tracheal placode (2013)
  • Author(s): Kondo T
  • Organizer: The 17th International Congress of Developmental Biology
  • Place of Presentation: カンクン、メキシコ
• [Presentation] 上皮構造の局所的不安定化による形態形成の制御 (2013)
  • Author(s): Hayashi S
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜市
• [Presentation] Apical extracellular matrix and its coupling with mebrane shape tracheal tube geometry in Drosophila (2013)
  • Author(s): Dong B
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜市
• [Presentation] A self-sustaining signaling center controls cell elongation (2013)
  • Author(s): Otani T
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜市
• [Presentation] Synergistic action of mitosis and cell shape change in epithelial invagination (2013)
  • Author(s): Hayashi S
  • Organizer: 第51回日本生物物理学会年会
  • Place of Presentation: 京都市
• [Presentation] 細胞外マトリクスとアピカル細胞膜のカップリングが気管上皮チューブの形状を決定する (2013)
  • Author(s): Hayashi S
  • Organizer: 第51回日本生物物理学会年会
  • Place of Presentation: 京都市
• [Presentation] 上皮形態形成と分裂期ダイナミクス (2013)
  • Author(s): Kondo T
  • Organizer: 日本発生生物学会 2013年秋期シンポジウム
  • Place of Presentation: 神戸市
• [Presentation] Cellular logic behind organ shape specification (2013)
  • Author(s): Hayashi S
  • Organizer: 大阪大学蛋白質研究所セミナー 細胞が集団になって初めて発現する機能
  • Place of Presentation: 大阪市
  • Invited
• [Presentation] 細胞外マトリクスとアピカル細胞膜のカップリングが気管上皮チューブの形状を決定する (2013)
  • Author(s): Hayashi S
  • Organizer: 第36回日本分子生物学会年会ワークショップ
  • Place of Presentation: 神戸市
• [Presentation] Cell and tissue morphogenesis in Drosophila (2012)
  • Author(s): 林茂生
  • Organizer: India-Japan Workshop
  • Place of Presentation: バンガロール、インド(招待講演)
  • Year and Date: 2012-1-9
• [Presentation] Force coupling in three-dimensional epithelial morphogenesis in Drosophila (2011)
  • Author(s): 林茂生
  • Organizer: 第49回日本生物物理学会年会
  • Place of Presentation: 姫路市(招待講演)
  • Year and Date: 2011-9-16
• [Presentation] エンドソームシャトリングによる細胞成長の制御 (2011)
  • Author(s): 林茂生
  • Organizer: 第5回膜生物学グローバルCOE研究討論会
  • Place of Presentation: 淡路市(招待講演)
  • Year and Date: 2011-7-21
• [Presentation] Mitotic cell rounding accelerates invagination of the Drosophila tracheal placode/分裂期進入に伴う細胞球形化がショウジョウバエ胚気管原基の陥入を促進する (2011)
  • Author(s): 近藤武史
  • Organizer: 第44回日本発生生物学会
  • Place of Presentation: 宜野湾市
  • Year and Date: 2011-5-19
• [Presentation] IKKepsilonはFascin/SingedをPKCによるリン酸化から保護することによってアクチンの束化を促進する (2011)
  • Author(s): 大谷哲久
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2011-12-15
• [Presentation] Mitotic Cell Rounding Accelerates Invagination of the Drosophila Tracheal Placode (2011)
  • Author(s): 近藤武史
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2011-12-13
• [Presentation] Regeneration of Polychaete Annellide, Perinereis nuntia Suggests a Homeogenetic Mechanisms of Sequential Segmentation Involving Wingless (2011)
  • Author(s): 林茂生
  • Organizer: The 21st CDB Meeting The 1st CDB-Regeneration Biology Study Group meeting "from Regeneration Biology to Regenerative Medicine (I)"
  • Place of Presentation: 神戸市
  • Year and Date: 2011-11-24
• [Presentation] Imaging and quantitative approaches or the study of epithelial morphogenesis in Drosophila (2011)
  • Author(s): 林茂生
  • Organizer: RIKEN-Taiwan National Science Council Workshop on Biomedical Imaging and Image Processing
  • Place of Presentation: 神戸市(招待講演)
  • Year and Date: 2011-11-18
• [Presentation] Coordination of Planar and Apico-Basal Forces during Invagination of Epithelial Placode. (2010)
  • Author(s): 林茂生
  • Organizer: ASCB/JSCB/Riken CDB Meeting
  • Place of Presentation: 京都市
  • Year and Date: 2010-9-23
• [Presentation] ECM産生細胞の形状変化が司る骨格の形態形成:ハエ成虫肢のBall-and-socket型間接 (2010)
  • Author(s): 田尻怜子
  • Organizer: 日本発生生物学会 夏季シンポジウム2010
  • Place of Presentation: 東京都
  • Year and Date: 2010-8-25
• [Presentation] 関節で向かい合う骨格の二面がぴったりと嵌り合う仕組み-昆虫の肢の発生学と比較形態学- (2010)
  • Author(s): 田尻怜子
  • Organizer: 日本進化学会第12回東京大会
  • Place of Presentation: 東京都
  • Year and Date: 2010-8-2
• [Presentation] IKKε regulates recycling endosome shuttling by phosphorylation of Nuf/Rad11FIP3. (2010)
  • Author(s): 大谷哲久
  • Organizer: 札幌国際がんシンポジウム2010
  • Place of Presentation: 札幌市
  • Year and Date: 2010-6-28
• [Presentation] Milton/dMiro mediated morphogenesis of giant mitochondria shapes extremely long sperm tails of Drosophila. (2010)
  • Author(s): 野口立彦
  • Organizer: 第43回日本発生生物学会年会
  • Place of Presentation: 京都市
  • Year and Date: 2010-6-23
• [Presentation] IKKε regulates recycling endosome shuttling by phosphorylation of Nuf/Rad11FIP3. (2010)
  • Author(s): 大谷哲久
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-12-8
• [Presentation] Joint structure in the insect leg : development, evolution and Notch-mediated regulation (2010)
  • Author(s): 田尻怜子
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-12-8
• [Presentation] Regulation and function of Notch endosomal trafficking (2010)
  • Author(s): 林茂生
  • Organizer: 第5回Notch研究会
  • Place of Presentation: 東京都
  • Year and Date: 2010-11-8
• [Presentation] Joint structure in the insect leg : development, evolution and Notch-mediated regulation (2010)
  • Author(s): 田尻怜子
  • Organizer: 第5回Notch研究会
  • Place of Presentation: 東京都
  • Year and Date: 2010-11-8
• [Remarks] 細胞をドーナツ型に変形させる力の源 －上皮細胞のトポロジーを変換するメカニズムを解明－
• [Remarks] 細胞伸長の司令塔を配置する仕組みを解明 －細胞内の物流システムの調節に新たな知見－
• [Remarks] ドーナツ型？！奇抜な細胞の形態変化を可能にする仕組み
• [Remarks] 細胞伸長の司令塔分子を正しく配置するメカニズム
• [Remarks] アクチン繊維の自己組織化が管の形を整える
• [Remarks]
  • URL: http://www.riken.jp/r-world/research/lab/cdb/mor/index.html
• [Remarks]
  • URL: http://www.cdb.riken.jp/jp/02_research/0201_core06.html
• [Remarks]
  • URL: http://www.cdb.riken.jp/signal/
• [Remarks]
  • URL: http://www.cdb.riken.jp/signal/