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

Publication date: 13 March 2017
Source:Developmental Cell, Volume 40, Issue 5
Author(s): Katsura Minegishi, Masakazu Hashimoto, Rieko Ajima, Katsuyoshi Takaoka, Kyosuke Shinohara, Yayoi Ikawa, Hiromi Nishimura, Andrew P. McMahon, Karl Willert, Yasushi Okada, Hiroshi Sasaki, Dongbo Shi, Toshihiko Fujimori, Toshihisa Ohtsuka, Yasunobu Igarashi, Terry P. Yamaguchi, Akihiko Shimono, Hidetaka Shiratori, Hiroshi Hamada
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.

Graphical abstract

Teaser

Polarization of node cells along the anterior-posterior axis of mouse embryos is responsible for left-right symmetry breaking. 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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