title: Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/beta catenin and Wnt/PCP activities, through interaction with the Dally-like homolog Knypek.
abstract: Dickkopf-1 (Dkk1) is a secreted protein that negatively modulates the Wnt/beta catenin pathway. Lack of Dkk1 function affects head formation in frog and mice, supporting the idea that Dkk1 acts as a "head inducer" during gastrulation. We show here that lack of Dkk1 function accelerates internalization and rostral progression of the mesendoderm and that gain of function slows down both internalization and convergence extension, indicating a novel role for Dkk1 in modulating these movements. The motility phenotype found in the morphants is not observed in embryos in which the Wnt/beta catenin pathway is overactivated, and that dominant-negative Wnt proteins are not able to rescue the gastrulation movement defect induced by absence of Dkk1. These data strongly suggest that Dkk1 is acting in a beta catenin independent fashion when modulating gastrulation movements. We demonstrate that the glypican 4/6 homolog Knypek (Kny) binds to Dkk1 and that they are able to functionally interact in vivo. Moreover, Dkk1 regulation of gastrulation movements is kny dependent. Kny is a component of the Wnt/planar cell polarity (PCP) pathway. We found that indeed Dkk1 is able to activate this pathway in both Xenopus and zebrafish. Furthermore, concomitant alteration of the beta catenin and PCP activities is able to mimic the morphant accelerated cell motility phenotype. Our data therefore indicate that Dkk1 regulates gastrulation movement through interaction with LRP5/6 and Kny and coordinated modulations of Wnt/beta catenin and Wnt/PCP pathways.
authors.affiliation: Medical Research Council Centre for Developmental Neurobiology, King's College London, SE1 1UL London, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Caneparo
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Huang
authors.forename: Nicole
authors.initials: N
authors.lastname: Staudt
authors.forename: Masasumi
authors.initials: M
authors.lastname: Tada
authors.forename: Reiner
authors.initials: R
authors.lastname: Ahrendt
authors.forename: Olga
authors.initials: O
authors.lastname: Kazanskaya
authors.forename: Christof
authors.initials: C
authors.lastname: Niehrs
authors.forename: Corinne
authors.initials: C
authors.lastname: Houart
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000737:chemistry / Q000378:metabolism; D005775:Gastrula / Q000737:chemistry / Q000378:metabolism*; D053673:Glypicans / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin