Minegishi Katsura, Hashimoto Masakazu, Ajima Rieko, Takaoka Katsuyoshi, Shinohara Kyosuke, Ikawa Yayoi, Nishimura Hiromi, McMahon Andrew P, Willert Karl, Okada Yasushi, Sasaki Hiroshi, Shi Dongbo, Fujimori Toshihiko, Ohtsuka Toshihisa, Igarashi Yasunobu, Yamaguchi Terry P, Shimono Akihiko, Shiratori Hidetaka, Hamada Hiroshi
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.
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
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 Wnt5aWnt5b 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.
小鼠胚胎前后轴上节点细胞的极化负责左右对称的打破。然而，节点细胞如何极化一直未知。Wnt5a和Wnt5b相对于节点在后方表达，而Wnt信号的Sfrp抑制剂基因在前方表达。在这里我们表明，在Wnt5aWnt5b和Sfrp突变胚胎中，以及在Wnt5a或Sfrp1均匀分布的情况下，节点细胞的极化受损，这表明Wnt5和Sfrp蛋白在此过程中作为指导性信号起作用。单个细胞中平面细胞极性（PCP）核心蛋白Prickle1和Prickle2的缺失或Wnt5a的局部强制表达扰乱了相邻野生型细胞的极化。我们的结果表明，Wnt5a和Wnt5b及其Sfrp抑制剂的相反梯度，以及通过PCP蛋白的细胞间信号传导，使节点细胞沿前后轴极化以打破左右对称。
