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Dev Cell. 2017 Mar 13;40(5):439-452.e4. doi: 10.1016/j.devcel.2017.02.010.

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

Author information

1
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.
2
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
3
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.
4
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.
5
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
6
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
7
Laboratory for Cell Polarity Regulation, RIKEN Quantitative Biology Center, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.
8
Laboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
9
Division of Embryology, National Institute for Basic Biology, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.
10
Department of Biochemistry, Faculty of Medicine/Graduate School of Medicine, University of Yamanashi, 1110 Shimo-Kato, Chuo, Yamanashi 409-3898, Japan.
11
Advanced Software Development Department, OLYMPUS Software Technology Corporation, 2-3 Kuboyama-cho, Hachioji-shi, Tokyo 192-8512, Japan.
12
Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, MD 21702, USA.
13
Vertebrate Body Plan Group, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
14
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.

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.

KEYWORDS:

Sfrp; Wnt; basal body; breaking of left-right symmetry; cilia; planar cell polarity

PMID:
28292423
DOI:
10.1016/j.devcel.2017.02.010
[Indexed for MEDLINE]
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