プラナリアの再生組織構築を決定する位置情報システムの解明

2009 Fiscal Year Annual Research Report

• Project/Area Number: 17GS0318
• Research Institution: Kyoto University
• Principal Investigator: 阿形 清和 Kyoto University, 大学院・理学研究科, 教授 (70167831)
• Keywords: 器官形成 / 位置情報 / 脳 / プラナリア / 幹細胞 / マウス / ES細胞 / シグナル伝達

Research Abstract

器官形成のための位置情報をつくるにあたり、座標軸の方向性(極性:どちら側を頭側にして、どちら側を尾側にするのか)を決める必要がある。今年度には、モーガン以来100年の謎だった極性を作るためのメカニズムを明らかにした。Patched(ヘッジホック受容体)ホモログ遺伝子をRNA干渉法によって遺伝子ノックダウンするとプラナリアが再生する時に体の頭尾軸が逆転することを見いだした。これをきっかけとして極性をつくるメカニズムの解読に成功した。すなわち、Patchedのリガンドであるヘッジホックが頭部で合成され、腹側神経索にそって頭側から尾側の一方向に輸送されているとすると、切断した断片の尾側からヘッジホックが漏れ、それがWntシグナルを活性化することで、必ず元の尾側に尾が作られると理解された。すなわち、プラナリアは神経軸索の輸送の方向性が体の極性を決めていると考えられた。極性の成立に伴い、尾側でWntシグナルが活性されるのに対し、頭側ではERKシグナルが活性化され、頭尾軸にそった位置座標がつくられること。さらにnou-darakeファミリーがERKシグナルをモジュレートすることによって、頭尾軸にそった位置情報の中から、頭・首・咽頭・尾といった体の部位が形成されることを見出した。そして、各部位ごとに脳の原基や咽頭の原基が形成され、各原基の中でも体の極性に応じた位置情報がそれぞれ作られて器官形成がなされることを明らかにした。プラナリアの再生を用いて体全体の位置情報と各器官の位置情報をつくり基本原理を明らかにした。また、これらの位置情報をつくる原理をマウスES細胞にも適用して、マウス脳の一部を作ることに成功し、臓器再生への一歩を踏み出した。

Research Products

• [Journal Article] Cellular and molecular dissection of pluripotent adult somaticstem cells in planarians (2010)
  • Author(s): Norito Shibata, Labib Rouhana, Kiyokazu Agata
  • Journal Title: Develop.Growth Differ. 52 Pages: 27-41
  • Peer Reviewed
• [Journal Article] Single-cell gene profiling of planarian stem cells using fluorescent activated cell sorting and its "index sorting" function for stem cell research (2010)
  • Author(s): Tetsutaro Hayashi, Norito Shibata, Ryo Okumura, Tomomi Kudome, Osamu Nishimura, Hiroshi Tarui, Kiyokazu Agata
  • Journal Title: Develop.Growth Differ. 52 Pages: 131-144
  • Peer Reviewed
• [Journal Article] Analysis of motor function modulated by cholonergic neurins in planarian Dugesia japonica (2010)
  • Author(s): Kaneyasu Nishimura, Yoshihisa Kitamura, Takashi Taniguchi, Kiyokazu Agata
  • Journal Title: Neuroscience
  • Peer Reviewed
• [Journal Article] Different requirements for post-transcriptional regulators and translational initiation factors during planarian regeneration and stem cell maintenance (2010)
  • Author(s): Labib Rouhana, Norito Shibata, Kiyokazu Agata
  • Journal Title: Dev.Biol.
  • Peer Reviewed
• [Journal Article] Identification of a Novel Planarian G-Protein-Coupled Receptor That Responds to Serotonin in Xenopus laevis Oocytes (2009)
  • Author(s): Kaneyasu Nishimura, Kazuhiro Unemura, Jun Tsushima, Yosuke Yamauchi, Jun Otomo, Takashi Taniguchi, Shuji Kaneko, Kiyokazu Agata, Yoshihisa Kitamura
  • Journal Title: Biol.Pharm.Bull. 32(10) Pages: 1672-1677
  • Peer Reviewed
• [Journal Article] Planarians Maintain a Constant Ratio of Different Cell Types During Changes in Body Size by Using the Stem Cell System (2009)
  • Author(s): Hiroyuki Takeda, Kaneyasu Nishimura, Kiyokazu Agata
  • Journal Title: Zoological Science 26 Pages: 805-813
  • Peer Reviewed
• [Journal Article] Planarian Hedgehog/Patched establishes anterior-posterior polarity by regulating Wnt signaling (2009)
  • Author(s): Shigenobu Yazawa, Yoshihiko Umesono, Tetsutaro Hayashi, Hiroshi Tarui, Kiyokazu Agata
  • Journal Title: PNAS(Proceedings of the National Academy of Sciences of the United States of America) 106 Pages: 22329-22334
  • Peer Reviewed
• [Presentation] プラナリアおよびイモリの脳におけるドパミン神経再生機構に関する研究 (2010)
  • Author(s): Kaneyash Nishimura, Takeshi Inoue, Yoshihisa Kitamura, Kiyokazu Agata
  • Organizer: 第4回神経発生討論会
  • Place of Presentation: 岡崎市・岡崎コンファレンスセンター
  • Year and Date: 2010-03-19
• [Presentation] プラナリアにおけるアセチルコリン神経が制御する運動機能の解析 (2010)
  • Author(s): Kaneyash Nishimura, Yoshihisa Kitamura, Takashi Taniguchi, Kiyokazu Agata
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪市・大阪国際会議場
  • Year and Date: 2010-03-18
• [Presentation] Analysis of the molecular machanisms and neural network required for the photosensing behavior in planarian/プラナリアの走光性行動に関わる分子機構および神経回路の解析 (2009)
  • Author(s): Takeshi Inoue, Taiga Yamashita, Tomomi Takano, Kaneyasu Nishimura, Manami Fushiki, Kiyokazu Agata
  • Organizer: 日本分子生物学会第32回年会
  • Place of Presentation: 横浜市・パシフィコ横浜
  • Year and Date: 2009-12-12
• [Presentation] Integrated behavioral analysis and molecular analysis in planaria (2009)
  • Author(s): Taiga Yamashita, Takeshi Inoue, Kaneyasu Nishimura, Clement Lamy, Kiyokazu Agata
  • Organizer: 日本分子生物学会第32回年会
  • Place of Presentation: 横浜市・パシフィコ横浜
  • Year and Date: 2009-12-12
• [Presentation] Clarification of StemCell Reguratory Mechanism by piwi in Planarian/プラナリアでの piwi による全能性幹細胞の分化制御機構の解明 (2009)
  • Author(s): Taisuke Ishiko, Norito Shibata, Osamu Nishimura, Labib Rouhana, Kuniaki Saito, Mikiko Shiomi, Haruhiko Shiomi, Kiyokazu Agata
  • Organizer: 日本分子生物学会第32回年会
  • Place of Presentation: 横浜市・パシフィコ横浜
  • Year and Date: 2009-12-09
• [Presentation] Analysis of P2X mediated molecilar mechanism of mitotic control in planarian stem cell/P2Xを介したプラナリア幹細胞の分子的増殖制御機構の解析 (2009)
  • Author(s): Toshihide Sakurai, Norito Shibata, Kiyokazu Agata
  • Organizer: 日本分子生物学会第32回年会
  • Place of Presentation: 横浜市・パシフィコ横浜
  • Year and Date: 2009-12-09
• [Presentation] Regeneration in Planaria (2009)
  • Author(s): Kiyokazu Agata
  • Organizer: Frontiers in Stem Cells Regeneration Advanced Training Courese
  • Place of Presentation: Woods Hole, MA U.S.A.
  • Year and Date: 2009-10-07
• [Presentation] プラナリア脳におけるドパミン神経新生機序の解析 (2009)
  • Author(s): Kaneyash Nishimura, Takeshi Inoue, Yoshihisa Kitamura, Kanji Yoshimoto, Hiroshi Ikegaya, Takashi Taniguchi, Kiyokazu Agata
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋市・名古屋国際会議場
  • Year and Date: 2009-09-16
• [Presentation] Analysis of genes involved on post-transcriptional regulation of gene expression in planarians (2009)
  • Author(s): Labib Rouhana, Kiyokazu Agata
  • Organizer: 16th International Society of Devlopmental Biologists Congress 2009
  • Place of Presentation: Edinburgh, Scotland, UK
  • Year and Date: 2009-09-09
• [Presentation] Cellular and molecular dynamics of stem cell differentation during planarian regeneration (2009)
  • Author(s): Junichi Tasaki, Yoshihiko Umesono, Norito Shibata, Kazu Itomi, Osamu Nishimura, Yoshimichi Tabata, Fuyan Son, Nobuko Suzuki, Ryoko Araki, Masumi Abe, Kiyokazu Agata
  • Organizer: 16th International Society of Devlopmental Biologists Congress 2009
  • Place of Presentation: Edinburgh, Scotland, UK
  • Year and Date: 2009-09-09
• [Presentation] Molecular cascades along cell commitment to differentiation of pluripotent adult somatic stem cells in planarian, D.japonica (2009)
  • Author(s): Norito Shibata, Tetsutaro Hayashi, Max Brueck, Reiko Amikura, Satoru Kobayashi, Osamu Nishimura, Hiroshi Tarui, Kiyokazu Agata
  • Organizer: 42th Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 新潟市・朱鷺メッセ
  • Year and Date: 2009-05-30
• [Presentation] Requirement for Lim-homeobox gene(DjlimA)activity for proper morphologic events from the middle stage of planarian regeneration (2009)
  • Author(s): Tetsutaro Hayashi, Minako Motoishi, Asuka Momiyama, Kazu Itomi, Chiharu Tanegashima, Kiyokazu Agata, Hiroshi Tarui
  • Organizer: 42th Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 新潟市・朱鷺メッセ
  • Year and Date: 2009-05-30
• [Presentation] Molecular basis of anterior-posterior patterning during planarian regeneration (2009)
  • Author(s): Yoshihiko Umesono, Junichi Tasaki, Kazu Itomi, Yoshimichi Tabata, Fuyan Son, Nobuko Suzuki, Ryoko Araki, Masumi Abe, Kiyokazu Agata
  • Organizer: 42th Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 新潟市・朱鷺メッセ
  • Year and Date: 2009-05-29
• [Presentation] Genome Analysis of the Planaria Schmidtea mediterranea sheds light into the evolution of 7-transmembrane receptors in metazoans (2009)
  • Author(s): Clement Lamy, Osamu Nishimura, Eric Bobb, Sofia Ross, Alejandro Sanchez Alvarado, Kiyokazu Agata
  • Organizer: 42th Annual Meeting for the Japanese Society of evelopmental Biologists
  • Place of Presentation: 新潟市・朱鷺メッセ
  • Year and Date: 2009-05-29
• [Presentation] Cloning and expression of piwi-and vasa-related genes in the triclads Polycelis auriculata and Phagocata kawakatsui (2009)
  • Author(s): Martina Hrouda, Shigenobu Yzawa, Norito Shibata, Kiyokazu Agata
  • Organizer: 42th Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 新潟市・朱鷺メッセ
  • Year and Date: 2009-05-29
• [Presentation] Cellular and molecular dynamics of stem cell differentiation during planarian regeneration (2009)
  • Author(s): Junichi Tasaki, Yoshihiko Umesono, Norito Shibata, Kazu Itomi, Osamu Nishimura, Yoshimichi Tabata, Fuyan Son, Nobuko Suzuki, Ryoko Araki, Masumi Abe, Kiyokazu Agata
  • Organizer: 42th Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 新潟市・朱鷺メッセ
  • Year and Date: 2009-05-28
• [Book] Brain and Neural Networks (2009)
  • Author(s): Kaneyasu Nishimura, Hiroshi Yamamoto, Kiyokazu Agata, Yoshihisa Kitamura
  • Total Pages: 9
  • Publisher: Landes Bioscience
• [Remarks]
  • URL: http://mbd.biophys.kyoto-u.ac.jp