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PMID: 17322405 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/beta catenin and Wnt/PCP activities, through interaction with the Dally-like homolog Knypek.

Genes & development ·Vol. 21 ·No. 4 ·2007-02-15 ·Pages 465-80

Caneparo L, Huang YL, Staudt N, Tada M, Ahrendt R, Kazanskaya O, Niehrs C, Houart C

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.

MeSH Terms
Animals Body Patterning/genetics Cell Polarity/genetics Embryo, Nonmammalian/chemistry,metabolism Gastrula/chemistry,metabolism Glypicans/metabolism Heparan Sulfate Proteoglycans/analysis,genetics,metabolism Intercellular Signaling Peptides and Proteins/analysis,genetics,metabolism Transfection Wnt Proteins/metabolism Xenopus/embryology,genetics,metabolism Xenopus Proteins/analysis,genetics,metabolism Zebrafish/embryology,genetics,metabolism Zebrafish Proteins/analysis,genetics,metabolism beta Catenin/metabolism
Chemicals
Glypicans Heparan Sulfate Proteoglycans Intercellular Signaling Peptides and Proteins Wnt Proteins Xenopus Proteins Zebrafish Proteins beta Catenin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Caneparo Luca
Medical Research Council Centre for Developmental Neurobiology, King's College London, SE1 1UL London, UK.
Huang Ya-Lin
Staudt Nicole
Tada Masasumi
Ahrendt Reiner
Kazanskaya Olga
Niehrs Christof
Houart Corinne
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.406007
Published
2007-02-15
Pages
465-80
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1804334
Subset
IM
Grants
Medical Research Council · G9900989 · United Kingdom
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1101/gad.406007 PMC Full Text View journal details
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