title: Wnt5b-Ryk pathway provides directional signals to regulate gastrulation movement.
abstract: Noncanonical Wnts are largely believed to act as permissive cues for vertebrate cell movement via Frizzled (Fz). In addition to Fz, Wnt ligands are known to regulate neurite outgrowth through an alternative receptor related to tyrosine kinase (Ryk). However, Wnt-Ryk signaling during embryogenesis is less well characterized. In this study, we report a role for Wnt5b as an instructive cue to regulate gastrulation movements through Ryk. In zebrafish, Ryk deficiency impairs Wnt5b-induced Ca(2+) activity and directional cell movement. Wnt5b-Ryk signaling promotes polarized cell protrusions. Upon Wnt5b stimulation, Fz2 but not Ryk recruits Dishevelled to the cell membrane, suggesting that Fz2 and Ryk mediate separate pathways. Using co-culture assays to generate directional Wnt5b cues, we demonstrate that Ryk-expressing cells migrate away from the Wnt5b source. We conclude that full-length Ryk conveys Wnt5b signals in a directional manner during gastrulation.
authors.affiliation: Department of Biology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Shengda
authors.initials: S
authors.lastname: Lin
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Baye
authors.forename: Trudi A
authors.initials: TA
authors.lastname: Westfall
authors.forename: Diane C
authors.initials: DC
authors.lastname: Slusarski
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D054262:Gastrulation; D020869:Gene Expression Profiling; D006801:Humans; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051157:Frizzled Receptors; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C480282:Wnt5a protein, zebrafish; D029961:Zebrafish Proteins; C510284:fzd2 protein, zebrafish; D020794:Receptor Protein-Tyrosine Kinases; C551670:Ryk protein, zebrafish; D002118:Calcium