A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking.
A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking.
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DOI：
10.1016/j.devcel.2017.02.010
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发表时间：
2017-03-13
影响因子：
11.8
通讯作者：
Hamada H
中科院分区：
文献类型：
--
作者：
Minegishi K;Hashimoto M;Ajima R;Takaoka K;Shinohara K;Ikawa Y;Nishimura H;McMahon AP;Willert K;Okada Y;Sasaki H;Shi D;Fujimori T;Ohtsuka T;Igarashi Y;Yamaguchi TP;Shimono A;Shiratori H;Hamada H
小鼠胚胎前后轴上结节细胞的极化是左右对称性破坏的原因。然而，节点细胞是如何变得两极化的还不得而知。Wnt5a和Wnt5b在相对于节点的后面表达，而Wnt信号的SFRP抑制剂的基因在前面表达。在这里，我们发现在WNT5a−/−WNT5b−/−和sfrp突变胚胎中，节点细胞的极化受到损害，并且在Wnt5a或sfrp1均匀分布的情况下也是如此，这表明Wnt5和sfrp蛋白在这一过程中起着指导信号的作用。在单个细胞中缺乏平面细胞极性(PCP)核心蛋白Prickle1和Prickle2或局部强制表达Wnt5a会扰乱邻近野生型细胞的极化。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，使结节细胞沿前后轴极化，从而打破左右对称性。小鼠胚胎前后轴上结节细胞的极化是左右对称性破坏的原因。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，使节点细胞沿前后轴极化，打破左右对称性。
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. 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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