Origin of morphological asymmetries

• Project/Area Number: 17H01435
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Hamada Hiroshi 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (00208589)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000); Fiscal Year 2019: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000); Fiscal Year 2018: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000); Fiscal Year 2017: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
• Keywords: 胚発生 / 左右非対称性 / 繊毛 / 頭尾軸 / 母性因子 / エピジェネテイックス / カルシウム / 発生遺伝 / 着床前胚

Outline of Final Research Achievements

Our body has three axes, anterior-posterior (A-P), dorso-ventral (D-V), and left-right (L-R) axes. How are these body axes (polarities) determined during development? In this study, we will study the origin of L-R polarity and that of A-P polarity. For the L-R polarity, we will examine roles of motile and immotile cilia and how the directional fluid generated by motile cilia is sensed by the mouse embryo. As for the A-P polarity, we will investigate roles of maternal factors in establishing the A-P polarity and in cell lineage specification during pre-implantation.

Academic Significance and Societal Importance of the Research Achievements

体の極性の起源は発生生物学の基本命題である。左右の極性の起源には近年で大きな進展があったが、まだ多くの本質的な問題が残されている。頭尾の極性の起源については、他の生物では卵細胞に遡るが，哺乳動物では全く不明である。これらの問題を明らかにすることで、哺乳動物の体が形成される仕組みの理解に、大きな貢献をする。

Research Products

• [Int'l Joint Research] University of Munster(ドイツ)
• [Int'l Joint Research] National University of Singapore(シンガポール)
• [Int'l Joint Research] EPFL(スイス)
• [Int'l Joint Research] Yale University(米国)
• [Journal Article] Nodal paralogues underlie distinct mechanisms for visceral left-right asymmetry in reptiles and mammals (2020)
  • Author(s): Kajikawa Eriko、Horo Uzuki、Ide Takahiro、Mizuno Katsutoshi、Minegishi Katsura、Hara Yuichiro、Ikawa Yayoi、Nishimura Hiromi、Uchikawa Masanori、Kiyonari Hiroshi、Kuraku Shigehiro、Hamada Hiroshi
  • Journal Title: Nature Ecology & Evolution Volume: 4 Issue: 2 Pages: 261-269
  • DOI: 10.1038/s41559-019-1072-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Diversity of left-right symmetry breaking mechanisms among animals. (2020)
  • Author(s): Hamada, H. and Tam, P. P. L.
  • Journal Title: F1000 Research Volume: 9 Pages: 123-126
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ciliogenesis‐coupled accumulation of IFT‐B proteins in a novel cytoplasmic compartment (2019)
  • Author(s): Lamri Lynda、Twan Wang Kyaw、Katoh Takanobu A.、Botilde Yanick、Takaoka Katsuyoshi、Ikawa Yayoi、Nishimura Hiromi、Fukumoto Akemi、Minegishi Katsura、Mizuno Katsutoshi、Hamada Hiroshi
  • Journal Title: Genes to Cells Volume: 24 Issue: 11 Pages: 731-745
  • DOI: 10.1111/gtc.12722
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Simulation of the nodal flow of Dpcd and Rfx3 mutant embryo: comparison of mechano-sensing and morphogen transport hypotheses (2018)
  • Author(s): Toshihiro Omori, Katja Winter, Kyosuke Shinohara, Hiroshi Hamada, Takuji Ishikawa
  • Journal Title: Royal Society Open Science Volume: 5 Issue: 8 Pages: 180601-180601
  • DOI: 10.1098/rsos.180601
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters. (2018)
  • Author(s): Nabeshima R, Nishimura O, Maeda T, Shimizu N, Ide T, Yashiro K, Sakai Y, Meno C, Kadota M, Shiratori H, Kuraku S, Hamada H
  • Journal Title: Elife Volume: 7
  • DOI: 10.7554/elife.36435
  • Peer Reviewed / Open Access
• [Journal Article] Hyaluronan Works on the Right for Directional Gut Looping (2018)
  • Author(s): Hamada Hiroshi
  • Journal Title: Developmental Cell Volume: 46 Issue: 5 Pages: 525-526
  • DOI: 10.1016/j.devcel.2018.08.018
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Motion of An <b><i>Inv</i></b> Nodal Cilium: a Realistic Model Revealing Dynein-Driven Ciliary Motion with Microtubule Mislocalization (2018)
  • Author(s): Yu Yanan、Shinohara Kyosuke、Xu Huanming、Li Zhenfeng、Nishida Tomoki、Hamada Hiroshi、Xu Yuanqing、Zhou Jingqi、Shao Daisy、Li Xiangchen、Chen Duanduan
  • Journal Title: Cellular Physiology and Biochemistry Volume: 51 Issue: 6 Pages: 2843-2857
  • DOI: 10.1159/000496038
  • Peer Reviewed / Int'l Joint Research
• [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] 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] Both Nodal signalling and stochasticity select for prospective distal visceral endoderm in mouse embryos (2017)
  • Author(s): Takaoka Katsuyoshi、Nishimura Hiromi、Hamada Hiroshi
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 1492-1492
  • DOI: 10.1038/s41467-017-01625-x
  • Peer Reviewed
• [Presentation] Role of immotile cilia in flow sensing (2019)
  • Author(s): Hamada,H.
  • Organizer: FASEB Summer Research Conference on cilia
  • Int'l Joint Research / Invited
• [Presentation] Planar cell polarity for left-right asymmetry (2019)
  • Author(s): Hamada,H.
  • Organizer: Gordon Research Conference on Int signaling
  • Int'l Joint Research / Invited
• [Presentation] Cilia-dependent and independent mechanisms for left-right symmetry breaking among vertebrates (2019)
  • Author(s): Hiroshi Hamada
  • Organizer: Hunter Meeting 2019
  • Int'l Joint Research / Invited
• [Presentation] Role of Ca2+ in sensing fluid flow for left-right symmetry breaking (2019)
  • Author(s): Hiroshi Hamada
  • Organizer: FASEB, The Biology of Cilia and Flagella
  • Int'l Joint Research / Invited
• [Presentation] Role of Wnt signaling in positioning of the basal body (2019)
  • Author(s): Hiroshi Hamada
  • Organizer: Gordon Research Conference on Wnt signaling
  • Int'l Joint Research / Invited
• [Presentation] Readouts of fluid flow sensing by immotile cilia (2019)
  • Author(s): Hiroshi Hamada
  • Organizer: Cold Spring Harbor China Meeting: cilia and centrosome
  • Int'l Joint Research / Invited
• [Presentation] Left-right symmetry breaking in mouse embryo (2018)
  • Author(s): Hamada,H.
  • Organizer: Indian Society of Developmental Biology
  • Int'l Joint Research / Invited
• [Presentation] Motile and immotile cilia for left-right asymmetry (2018)
  • Author(s): Hamada,H.
  • Organizer: EMBO Workshop
  • Int'l Joint Research / Invited
• [Presentation] Imaging of Ca2+ signals in mouse embryos (2018)
  • Author(s): Hamada,H.
  • Organizer: EMBO Meeting on mouse embryo imaging
  • Int'l Joint Research / Invited
• [Presentation] Role of cilia in left-right symmetry breaking in mouse embryo (2018)
  • Author(s): Hamada,H.
  • Organizer: British Society of Developmental Biology
  • Int'l Joint Research / Invited
• [Presentation] Motile and immotile cilia in left-right symmetry breaking (2018)
  • Author(s): Hiroshi Hamada
  • Organizer: British Society of Developmental Biology
  • Int'l Joint Research / Invited
• [Presentation] Imaging of ciliary motility and calcium influx in mouse embryo (2018)
  • Author(s): Hiroshi Hamada
  • Organizer: EMBO Meeting on mouse embryo imaging
  • Int'l Joint Research / Invited
• [Presentation] Cilia-dependent and independent mechanisms for left-right symmetry breaking among vertebrates (2018)
  • Author(s): Hiroshi Hamada
  • Organizer: EMBO Workshop: Molecular mechanisms of developmental and regenera9ve biology
  • Int'l Joint Research / Invited
• [Presentation] Cilia-dependent and independent mechanisms for left-right symmetry breaking among vertebrates (2018)
  • Author(s): Hiroshi Hamada
  • Organizer: Indian Developmental Biology Society Meeting
  • Int'l Joint Research / Invited
• [Presentation] Role of immotile cilia in left-right symmetry breaking (2017)
  • Author(s): Hiroshi Hamada
  • Organizer: Gordon Research Conference: cilia, mucus,and mucociliary interactions
  • Int'l Joint Research / Invited
• [Presentation] Cilia in left-right symmetry breaking (2017)
  • Author(s): Hiroshi Hamada
  • Organizer: Cold Spring Harbor China Meeting: cilia and centrosome
  • Int'l Joint Research / Invited
• [Presentation] Left-right symmetry breaking in the mouse embryo (2017)
  • Author(s): Hiroshi Hamada
  • Organizer: International Societry for Developmental Biology 2017
  • Int'l Joint Research / Invited
• [Presentation] Role of immotile cilia in sensing fluid flow (2017)
  • Author(s): Hiroshi Hamada
  • Organizer: ASCB/EMBO Special Interest Subgroup (Cilia:Traffic, Signals, Disease)
  • Int'l Joint Research / Invited
• [Remarks] 哺乳類と鳥類の左右非対称性メカニズムの乖離を説明～爬虫類を利用して
  • URL: https://www.riken.jp/press/2020/20200109_1/index.html