title: A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking.
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.
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory for Organismal Patterning, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: katsura.minegishi@riken.jp.
authors.forename: Katsura
authors.initials: K
authors.lastname: Minegishi
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan; Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Rieko
authors.initials: R
authors.lastname: Ajima
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takaoka
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Shinohara
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory for Organismal Patterning, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Ikawa
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory for Organismal Patterning, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
authors.affiliation: Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Willert
authors.affiliation: Laboratory for Cell Polarity Regulation, RIKEN Quantitative Biology Center, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Laboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Shi
authors.affiliation: Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujimori
authors.affiliation: Department of Biochemistry, Faculty of Medicine/Graduate School of Medicine, University of Yamanashi, 1110 Shimo-Kato, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ohtsuka
authors.affiliation: Advanced Software Development Department, OLYMPUS Software Technology Corporation, 2-3 Kuboyama-cho, Hachioji-shi, Tokyo 192-8512, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Igarashi
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Yamaguchi
authors.affiliation: Vertebrate Body Plan Group, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shimono
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Shiratori
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory for Organismal Patterning, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: hiroshi.hamada@riken.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D019521:Body Patterning; D002450:Cell Communication; D016764:Cell Polarity; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein / Q000378:metabolism*; D000099274:Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D011506:Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D000099274:Frizzled-Related Proteins; C524253:Prickle1 protein, mouse; C518732:Prickle2 protein, mouse; C438615:Wnt5a protein, mouse; C468567:Wnt5b protein, mouse
keywords: Sfrp; Wnt; basal body; breaking of left-right symmetry; cilia; planar cell polarity