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A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node ells for Left-Right Symmetry Breaking

  1. Author:
    Minegishi, Katsura
    Hashimoto, Masakazu
    Ajima, Rieko
    Takaoka, Katsuyoshi
    Shinohara, Kyosuke
    Ikawa, Yayoi
    Nishimura, Hiromi
    McMahon, Andrew P.
    Willert, Karl
    Okada, Yasushi
    Sasaki, Hiroshi
    Shi, Dongbo
    Fujimori, Toshihiko
    Ohtsuka, Toshihisa
    Igarashl, Yasunobu
    Yamaguchi, Terry
    Shimono, Akihiko
    Shiratori, Hidetaka
    Hamada, Hiroshi

  2. Author Address

    Osaka Univ, Grad Sch Frontier Biosci, Dev Genet Grp, 1-3 Yamada Oka, Suita, Osaka 5650871, Japan.RIKEN, Ctr Dev Biol, Lab Organismal Patterning, Chuo Ku, 2-2-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan.NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.Univ Southern Calif, Keck Sch Med, Dept Stem Cell Biol & Regenerat Med, Los Angeles, CA 90033 USA.Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.RIKEN, Quantitat Biol Ctr, Lab Cell Polar Regulat, 6-2-3 Furuedai, Suita, Osaka 5650874, Japan.Osaka Univ, Grad Sch Frontier Biosci, Lab Embryogenesis, 1-3 Yamada Oka, Suita, Osaka 5650871, Japan.Natl Inst Basic Biol, Div Embryol, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan.Univ Yamanashi, Grad Sch Med, Dept Biochem, Fac Med, 1110 Shimo Kato, Chuo, Yamanashi 4093898, Japan.OLYMPUS Software Technol Corp, Adv Software Dev Dept, 2-3 Kuboyama Cho, Hachioji, Tokyo 1928512, Japan.RIKEN, Ctr Dev Biol, Vertebrate Body Plan Grp, Chuo Ku, 2-2-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan.Natl Inst Genet, Yata 1111, Mishima, Shizuoka 4118540, Japan.Max Planck Inst Biophys Chem, Fassberg 11, D-37077 Gottingen, Germany.Tokyo Univ Agr & Technol, Inst Engn, Koganei, Tokyo 1848588, Japan.Heidelberg Univ, Ctr Organismal Studies, D-89120 Heidelberg, Germany.Bristol Myers Squibb, Shinji Ku, 6-5-1 Nishi Shinjiku, Tokyo 1631328, Japan.Kyoto Sangyo Univ, Fac Life Sci, Kita Ku, Kyoto 6038555, Japan.
    1. Year: 2017
    2. Date: Mar 13
  2. Journal: DEVELOPMENTAL CELL
  3. CELL PRESS,
    1. 40
    2. 5
    3. Pages: 439-452
  5. Type of Article: Article
  6. ISSN: 1534-5807
  1. Abstract:

    Polarization of node cells along the anterior-posterior axis of mouse embryos is responsible for left-right symmetry breaking. How node cells become polarized has remained unknown, however. Wnt5a and Wnt5b are expressed posteriorly relative to the node, whereas genes for Sfrp inhibitors of Wnt signaling are expressed anteriorly. Here we show that polarization of node cells is impaired in Wnt5a(-/-)Wnt5b(-/-) and Sfrp mutant embryos, and also in the presence of a uniform distribution of Wnt5a or Sfrp1, suggesting that Wnt5 and Sfrp proteins act as instructive signals in this process. The absence of planar cell polarity (PCP) core proteins Prickle1 and Prickle2 in individual cells or local forced expression of Wnt5a perturbed polarization of neighboring wild-type cells. Our results suggest that opposing gradients of Wnt5a and Wnt5b and of their Sfrp inhibitors, together with intercellular signaling via PCP proteins, polarize node cells along the anterior-posterior axis for breaking of left-right symmetry.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.devcel.2017.02.010
  3. View record in Web of Science®
  4. WOS: 000396966000005

Library Notes

  1. Fiscal Year: FY2016-2017
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