Role of motile and immotile cilia in left-right symmetry breaking

• Project Area: Cilium-centrosome system regulating biosignal flows
• Project/Area Number: 24113004
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research (2016-2017); Osaka University (2012-2015)
• Principal Investigator: Hamada Hiroshi 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 (00208589)
• Co-Investigator(Kenkyū-buntansha): 広野 雅文 法政大学, 生命科学部, 教授 (10212177) ; 岸本 健雄 お茶の水女子大学, サイエンス&エデュケーションセンター, 客員教授 (00124222)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥277,810,000 (Direct Cost: ¥213,700,000、Indirect Cost: ¥64,110,000); Fiscal Year 2016: ¥50,830,000 (Direct Cost: ¥39,100,000、Indirect Cost: ¥11,730,000); Fiscal Year 2015: ¥52,520,000 (Direct Cost: ¥40,400,000、Indirect Cost: ¥12,120,000); Fiscal Year 2014: ¥51,090,000 (Direct Cost: ¥39,300,000、Indirect Cost: ¥11,790,000); Fiscal Year 2013: ¥52,390,000 (Direct Cost: ¥40,300,000、Indirect Cost: ¥12,090,000); Fiscal Year 2012: ¥70,980,000 (Direct Cost: ¥54,600,000、Indirect Cost: ¥16,380,000)
• Keywords: 発生制御 / 発生・分化 / 左右非対称性 / 繊毛 / 水流 / 発現制御

Outline of Final Research Achievements

We have revealed how left-right asymmetry of our body is established during development. In particular, we have clarified the following questions about node cilia, cilia that break left-right symmetry: 1) how node cilia are formed correctly with posterior tilt, 2) how node cilia acquire motility, 3) why node cilia can rotate unlike other cilia such as those in the airway, 4) how embryos sense the uni-directional fluid flow that is generated by rotating cilia.

Research Products

• [Int'l Joint Research] University of Munster/Hohenheim University(ドイツ)
• [Int'l Joint Research] 北京工科大学(中国)
• [Int'l Joint Research] John's Hopkins大学(米国)
• [Int'l Joint Research] ケンブリッジ大学(英国)
• [Int'l Joint Research] University of Munster/Hohenheim University(ドイツ)
• [Int'l Joint Research] 北京工科大学(中国)
• [Int'l Joint Research] John's Hopkins 大学(米国)
• [Int'l Joint Research] ケンブリッジ大学(英国)
• [Journal Article] Cilia in Left-Right Symmetry Breaking (2017)
  • Author(s): Kyosuke Shinohara, Hiroshi Hamada
  • Journal Title: Cold Spring Harbor Laboratory Perspectives in Biology Volume: 9 Issue: 10 Pages: 1-10
  • DOI: 10.1101/cshperspect.a028282
  • Peer Reviewed
• [Journal Article] Overall architecture of the IFT-B complex containing Cluap1/IFT38 as an essential component of the IFT-B peripheral subcomplex. (2016)
  • Author(s): Katoh, Y., Terada, M., Nishijima, Y., Takei, R., Nozaki, S., Hamada, H. and Nakayama, K.
  • Journal Title: J. Biol. Chem. Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Absence of radial spokes in mouse node cilia is required for rotational movement but confers ultrastructural instability as a trade-off. (2015)
  • Author(s): Shinohara, K., Chen, D., Nishida, T., Misaki, K., Yonemura, S. and Hamada, H.
  • Journal Title: Dev Cell Volume: 35 Issue: 2 Pages: 236-246
  • DOI: 10.1016/j.devcel.2015.10.001
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of physical forces in embryonic development. (2015)
  • Author(s): Hamada, H.
  • Journal Title: Seminars in Cell and Dev. Biol. Volume: 47/48 Pages: 88-91
  • DOI: 10.1016/j.semcdb.2015.10.011
  • Peer Reviewed / Acknowledgement Compliant
• [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] RBM14 prevents assembly of centriolar protein complexes and maintains mitotic spindle integrity (2015)
  • Author(s): Shiratsuchi, G., Takaoka, K., Ashikawa, T., Hamada H. and Kitagawa, D.
  • Journal Title: EMBO J. Volume: 34 Pages: 97-114
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Situs inversus and ciliary abnormalities: 20 years later, what is the connection? (2015)
  • Author(s): Pennekamp, P., Menchen, T., Dworniczak, B. and Hamada, H.
  • Journal Title: Cilia Volume: 4 Issue: 1 Pages: 1-1
  • DOI: 10.1186/s13630-014-0010-9
  • 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
• [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] Mechanisms of left-right asymmetry and patterning: Driver, mediator and responder. (2014)
  • Author(s): Hamada,H. and Tam, P.P. L.
  • Journal Title: F1000 Prime Reports Volume: 6 Pages: 110-110
  • DOI: 10.12703/p6-110
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The origin of cellular asymmetry in pre-implantation mouse embryo: a hypothesis. (2014)
  • Author(s): Takaoka, K. and Hamada, H.
  • Journal Title: Philos. Trans. Roy. Soc. B. Volume: 369 Issue: 1657 Pages: 1657-1657
  • DOI: 10.1098/rstb.2013.0536
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cilia, fluid flow, and Ca2+ signal in left-right symmetry breaking (2014)
  • Author(s): Yoshiba, S. and Hamada, H.
  • Journal Title: Trends in Genetics Volume: 30 Issue: 1 Pages: 10-17
  • DOI: 10.1016/j.tig.2013.09.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pih1d3 is required for cytoplasmic preassembly of axonemal dynein in mouse sperm. (2014)
  • Author(s): Dong, F., Shinohara, K., Nabeshima, R., Botilde, Y., Asai, Y., Fukumoto, A., Hasegawa, T., Matsuo, M., Takeda, H., Shiratori, H., Nakamura T., and Hamada, H.
  • Journal Title: J. Cell Biol. Volume: 204 Issue: 2 Pages: 203-213
  • DOI: 10.1083/jcb.201304076
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Asymmetric rotational stroke in mouse node cilia during left-right determination. (2013)
  • Author(s): Takamatsu, A.*, Ishikawa, T. Shinohara, K., and Hamada, H.
  • Journal Title: Physical Review E. Volume: 87 Pages: 050701-050701
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cluap1 localizes preferentially to the base and tip of cilia and is required for ciliogenesis in the mouse embryo (2013)
  • Author(s): Botilde, Y., Yoshiba, S., Shinohara, K., Hasegawa, T., Nishimura, H., Shiratori, H. and Hamada, H.
  • Journal Title: Developmental Biology Volume: 381 Issue: 1 Pages: 203-212
  • DOI: 10.1016/j.ydbio.2013.05.024
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Hydrodynamic phase synchronization in mouse node cilia. (2013)
  • Author(s): Takamatsu, A.*, Shinohara, K., Ishikawa, T. and Hamada, H.
  • Journal Title: Physical Review Letters Volume: 110 Pages: 248107-248107
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cilia at the Node of Mouse Embryos Sense Fluid Flow for Left-Right Determination via Pkd2 (2012)
  • Author(s): Yoshiba S, Shiratori H, Kuo IY, Kawasumi A, Shinohara K, Nonaka S, Asai Y, Sasaki G, Belo JA, Sasaki H, Nakai J, Dworniczak B, Ehrlich BE, Pennekamp P, Hamada H
  • Journal Title: Science Volume: 338(6104):226-3 Issue: 6104 Pages: 226-231
  • DOI: 10.1126/science.1222538
  • Peer Reviewed
• [Journal Article] Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA in the mouse embryo (2012)
  • Author(s): Nakamura, T., Saito, D., Kawasumi, A., Shinohara, K., Asai, Y., Takaoka, K., Dong, F., Takamatsu, A., Belo, J.A., Mochizuki, A., and Hamada, H.
  • Journal Title: Nat.Communic Volume: 3 Issue: 1 Pages: 1322-1322
  • DOI: 10.1038/ncomms2319
  • Peer Reviewed
• [Presentation] Left-right symmetry breaking in vertebrates (2018)
  • Author(s): Hiroshi Hamada
  • Organizer: 2nd CU FPhS-Riken CDB Synposium
  • Int'l Joint Research / Invited
• [Presentation] Role of motile and immotile cilia in left-right symmetry breaking (2017)
  • Author(s): Hiroshi Hamada
  • Organizer: International Society of Developmental Biology
  • Int'l Joint Research / Invited
• [Presentation] Role of immotile cilia in sensing fluid flow for left-right symmetry breaking (2017)
  • Author(s): Hiroshi Hamada
  • Organizer: 2017 American Society of Cell Biology/EMBO Meeting
  • Int'l Joint Research / Invited
• [Presentation] 体の非対称性：シグナルリングから繊毛へ (2015)
  • Author(s): Hamada, H.
  • Organizer: 第３８回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Role of Maternal Nodal signaling in pre-implantation development (2015)
  • Author(s): Hamada H.
  • Organizer: Mouse Molecular Genetics
  • Place of Presentation: Hinxton, UK
  • Year and Date: 2015-09-16
  • Int'l Joint Research / Invited
• [Presentation] Role of motile and immotile cilia in left-right asymmetry (2015)
  • Author(s): Hamada, H.
  • Organizer: Keystone Symposia (Heart Disease and Regeneration: Insights from Development)
  • Place of Presentation: Copper Mountain, Colorado, USA
  • Year and Date: 2015-03-01 – 2015-03-06
  • Invited
• [Presentation] Role of motile and immotile cilia in left-right symmetry breaking (2015)
  • Author(s): Hamada, H.
  • Organizer: Gordon Research Conference (CILIA, MUCUS & MUCOCILIARY INTERACTIONS)
  • Place of Presentation: Galveston, Texas, USA
  • Year and Date: 2015-02-08 – 2015-02-12
  • Invited
• [Presentation] Polarization of node cells by asymmetric Wnt5 distribution (2013)
  • Author(s): Hamada, H.
  • Organizer: OIST Conference (Gradients and Signaling)
  • Place of Presentation: Okinawa, Japan
  • Year and Date: 2013-11-11 – 2013-11-15
  • Invited
• [Presentation] Generating and sensing the flow signal for establishing left-right asymmetry (2013)
  • Author(s): Hamada, H.
  • Organizer: Annual Meeting of Korean Physiology Society
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2013-10-23 – 2013-10-25
  • Invited
• [Presentation] Multiple roles of cilia in left-right symmetry breaking (2013)
  • Author(s): Hamada, H.
  • Organizer: The 7th TAKAO Symposium
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2013-07-13 – 2013-07-15
  • Invited
• [Presentation] Origin of the anterior-posterior polarity of the mouse embryo (2013)
  • Author(s): Hamada, H.
  • Organizer: CDB Symposium 2013 (making of a vertebrate)
  • Place of Presentation: CDB, Kobe
  • Invited
• [Presentation] Role of motile and immotile cilia in left-right symmetry breaking (2013)
  • Author(s): Hamada, H.
  • Organizer: International Joint Meeting of the German Society for Cell Biology and the German Society for Developmental Biology
  • Place of Presentation: Heidelberg, Germany
  • Invited
• [Presentation] Development of left-right asymmetry in the mouse embryo (2013)
  • Author(s): Hamada, H.
  • Organizer: Instem Mouse Embryology Symposium
  • Place of Presentation: Bangalore, India
  • Invited
• [Presentation] Role of motile and immotile cilia in left-right symmetry breaking (2013)
  • Author(s): Hamada, H.
  • Organizer: 65th Annual Meeting of Korean Society of Physiology
  • Place of Presentation: Seoul, Korea
  • Invited
• [Presentation] Polorization of node cells by asymmetric Wnt signaling in the mouse embryo (2013)
  • Author(s): Hamada, H.
  • Organizer: OIST conference: Gradient and Signaling
  • Place of Presentation: OIST, Okinawa
  • Invited
• [Remarks] 体の左右を決める繊毛の構造解析と 繊毛が回転運動するしくみを解明
  • URL: http://www.alphagalileo.org/ViewItem.aspx?ItemId=159704&CultureCode=ja
• [Remarks] 理化学研究所・多細胞システム形成研究所、個体パターニング研究チーム
  • URL: http://www.cdb.riken.jp/research/laboratory/hamada.html
• [Remarks] 『新学術領域研究』シリア・中心体系による生体情報フローの制御
  • URL: http://www.nig.ac.jp/labs/NigPrjct/cilia-centrosome/index.html
• [Remarks] Hamada lab
  • URL: http://www.fbs.osaka-u.ac.jp/labs/hamada/
• [Remarks] Hamada Lab
  • URL: http://www.fbs.osaka-u.ac.jp/labs/hamada/publication.html