Ror2 Receptor Mediates Wnt11 Ligand Signaling and Affects Convergence and Extension Movements in Zebrafish
Ror2 Receptor Mediates Wnt11 Ligand Signaling and Affects Convergence and Extension Movements in Zebrafish
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DOI：
10.1074/jbc.m114.586099
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发表时间：
2014-07-25
影响因子：
4.8
通讯作者：
Zhou, Jianfeng
中科院分区：
文献类型：
--
作者：
Bai, Yan;Tan, Xungang;Zhou, Jianfeng
受体酪氨酸激酶Ror 2作为Wnt 5a的替代受体或共受体，介导小鼠和非洲爪蟾胚胎发生期间Wnt 5a诱导的会聚延伸运动，以及发育期间几种细胞类型的极性和迁移。然而，很少有人知道Ror 2的功能是保守的，在其他脊椎动物或参与其他非典型的Wnt配体在体内。在这项研究中，我们证明了斑马鱼胚胎中显性负性ror 2（ror 2-TM）mRNA的过表达会导致会聚和伸展缺陷以及眼睛不完全分离，这与slb/wnt 11突变体或wnt 11敲除变形子的观察结果一致。此外，在斑马鱼胚胎中共注射ror 2-TM mRNA和wnt 11吗啡基或ror 2和wnt 11共表达协同诱导了更严重的会聚和延伸缺陷。移植研究进一步表明，Ror 2受体响应于Wnt 11配体，并在原肠胚形成过程中调节细胞迁移和细胞形态。DnRor 2抑制Wnt 11的作用，这通过Wnt 11诱导的会聚和伸展缺陷的百分比降低来揭示。Ror 2与Wnt 11相互作用。Ror 2的胞内Tyr-647和Ser-863位点对于介导Wnt 11的作用是必不可少的。Dishevelled和RhoA作用于Wnt 11-Ror 2的下游以调节会聚和伸展运动。总的来说，我们的数据表明Ror 2在介导Wnt 11信号传导和调节斑马鱼的会聚和伸展运动中起着重要作用。
The receptor-tyrosine kinase Ror2 acts as an alternative receptor or co-receptor for Wnt5a and mediates Wnt5a-induced convergent extension movements during embryogenesis in mice and Xenopus as well as the polarity and migration of several cell types during development. However, little is known about whether Ror2 function is conserved in other vertebrates or is involved in other non-canonical Wnt ligands in vivo. In this study we demonstrated that overexpression of dominant-negative ror2 (ror2-TM) mRNA in zebrafish embryos resulted in convergence and extension defects and incompletely separated eyes, which is consistent with observations from slb/wnt11 mutants or wnt11 knockdown morphants. Moreover, the co-injection of ror2-TM mRNA and a wnt11 morpholino or the coexpression of ror2 and wnt11 in zebrafish embryos synergetically induced more severe convergence and extension defects. Transplantation studies further demonstrated that the Ror2 receptor responded to the Wnt11 ligand and regulated cell migration and cell morphology during gastrulation. DnRor2 inhibited the action of Wnt11, which was revealed by a decreased percentage of Wnt11-induced convergence and extension defects. Ror2 physically interacts with Wnt11. The intracellular Tyr-647 and Ser-863 sites of Ror2 are essential for mediating the action of Wnt11. Dishevelled and RhoA act downstream of Wnt11-Ror2 to regulate convergence and extension movements. Overall, our data suggest an important role of Ror2 in mediating Wnt11 signaling and in regulating convergence and extension movements in zebrafish.