Developmental Cell
Volume 40, Issue 5, 13 March 2017, Pages 439-452.e4
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Article
A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking

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Highlights

  • A gradient of Wnt5 activity polarizes node cells along the A-P axis

  • A Wnt5 activity asymmetry induces polarized localization of PCP proteins

  • Prickle proteins play a non-cell-autonomous role acting downstream of Wnt5a asymmetry

Summary

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

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

Cited by (0)

12

Present address: National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan

13

Present address: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany

14

Present address: Institute of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan

15

Present address: Centre for Organismal Studies, Heidelberg University, Heidelberg 69120, Germany

16

Present address: Bristol-Myers Squibb, 6-5-1 Nishi-Shinjiku, Shinjiku, Tokyo 163-1328, Japan

17

Present address: Faculty of Life Science, Kyoto Sangyo University, Kamigamo, Kita-ku, Kyoto 603-8555, Japan

18

Lead Contact