Analysis of the molecular mechanisms downstream of Pitx2 and left-right asymmetric morphogenesis.

• Project/Area Number: 26440124
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Kyoto Sangyo University (2016-2017); Osaka University (2014-2015)
• Principal Investigator: SHIRATORI Hidetaka 京都産業大学, 総合生命科学部, 教授 (90362590)
• Research Collaborator: HAMADA Hiroshi ; MINEGISHI Katsura ; IKAWA Yayoi
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 左右非対称 / 器官形成 / Pitx2 / 四肢形成 / 細胞外マトリックス / 左右軸 / 四肢

Outline of Final Research Achievements

About left-right asymmetric morphogenesis in visceral organs and limb, I discovered the following molecular mechanisms:
(1)In the limb, Pitx2 regulates left-right asymmetric morphogenesis. It was suggested that asymmetric morphogenesis may be involved in human handedness.
(2)LR1, a extracellular matrix factor, is involved in left-right asymmetric morphogenesis. It was suggested that the extracellular matrix is important for the left-right asymmetric morphogenesis.

Research Products

• [Int'l Joint Research] Institute of Medical Biology, A*STAR(シンガポール)
• [Int'l Joint Research] Institute of Medical Biology, A*STAR(シンガポール)
• [Int'l Joint Research] University Hospital Muenster(ドイツ)
• [Int'l Joint Research] Institute of Medical Biology, A*STAR(シンガポール)
• [Int'l Joint Research] Queen Mary University of London(英国)
• [Journal Article] A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking. (2017)
  • Author(s): Minegishi, K., Hashimoto, M., Ajima, R., Takaoka, K., Shinohara, K., Ikawa, Y., Nishimura, H., McMahon, AP., Willert, K., Okada, Y., Sasaki, H., Shi, D., Fujimori, T., Ohtsuka, T., Igarashi, Y., Yamaguchi, TP., Shimono, A., Shiratori, H., Hamada, H.
  • Journal Title: Dev Cell. Volume: 40 Issue: 5 Pages: 439-452
  • DOI: 10.1016/j.devcel.2017.02.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization. (2016)
  • Author(s): Wallmeier J, Shiratori H, Dougherty GW, Edelbusch C, Hjeij R, Loges NT, Menchen T, Olbrich H, Pennekamp P, Raidt J, Werner C, Minegishi K, Shinohara K, Asai Y, Takaoka K, Lee C, Griese M, Memari Y, Durbin R, Kolb-Kokocinski A, Sauer S, Wallingford JB, Hamada H, Omran H.
  • Journal Title: Am J Hum Genet. Volume: 4;99(2) Issue: 2 Pages: 460-469
  • DOI: 10.1016/j.ajhg.2016.06.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo (2015)
  • Author(s): Ioannis Kokkinopoulos, Hidekazu Ishida, Rie Saba, Prashant Ruchaya, Claudia Cabrera, Monika Struebig, Michael Barnes, Anna Terry, Masahiro Kaneko, Yasunori Shintani, Steven Coppen, Hidetaka Shiratori, Torath Ameen, Charles Mein, Hiroshi Hamada, Ken Suzuki, Kenta Yashiro
  • Journal Title: PLos One Volume: 10(10) Issue: 10 Pages: e0140831-e0140831
  • DOI: 10.1371/journal.pone.0140831
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Self-regulated left-right asymmetric expression of Pitx2c in the developing limb (2014)
  • Author(s): Shiratori, H., Yashiro, Iwai, N., Oki, S., Ikawa, Y., Kanata, K., and Hamada, H.
  • Journal Title: Dev. Biol. Volume: 395 Issue: 2 Pages: 331-341
  • DOI: 10.1016/j.ydbio.2014.09.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TGFβ signaling in establishing left-right asymmetry (2014)
  • Author(s): Shiratori, H. and Hamada, H.
  • Journal Title: Seminar in Cell & Dev. Biol. Volume: 32 Pages: 80-84
  • DOI: 10.1016/j.semcdb.2014.03.029
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Wnt5a/5bとWntのインヒビターの非対称な分布がノードの細胞極性を決めている (2015)
  • Author(s): 峰岸 かつら, 橋本 昌和, 安島 理恵子, 五十嵐 康伸, 篠原 恭介, 白鳥 秀卓, 濱田 博司
  • Organizer: 第３８回日本分子生物学会年会
  • Place of Presentation: 神戸ポートピアホテル（兵庫県神戸市）
  • Year and Date: 2015-12-04
  • Invited
• [Presentation] マウス発生中の四肢におけるPitx2の左右非対称な発現 (2014)
  • Author(s): 白鳥秀卓、濱田博司
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-26
• [Remarks] 大阪大学生命機能研究科発生遺伝学研究室ホームページ
  • URL: http://www.fbs.osaka-u.ac.jp/labs/hamada/