title: Ror2 receptor mediates Wnt11 ligand signaling and affects convergence and extension movements in zebrafish.
abstract: 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. Theintracellular Tyr-647andSer-863 sites ofRor2are 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.forename: Xungang
authors.initials: X
authors.lastname: Tan
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Chengdong
authors.initials: C
authors.lastname: Liu
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhao
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: Yunzhang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D000072261:Dishevelled Proteins; D005775:Gastrula / Q000166:cytology / Q000196:embryology*; D054262:Gastrulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D051153:Wnt Proteins; C092568:Wnt11 protein, zebrafish; D029961:Zebrafish Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D020559:Monomeric GTP-Binding Proteins; C549425:rhoab protein, zebrafish