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

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


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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Body Patterning*
  • Cell Communication
  • Cell Polarity*
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Mutant Strains
  • Models, Biological
  • Proteins / metabolism
  • Signal Transduction*
  • Wnt Proteins / metabolism*
  • Wnt-5a Protein / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Membrane Proteins
  • Prickle1 protein, mouse
  • Prickle2 protein, mouse
  • Proteins
  • WD repeat containing planar cell polarity effector
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • Wnt5b protein, mouse