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Genes Dev
2007 Feb 15;214:465-80. doi: 10.1101/gad.406007.
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Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/beta catenin and Wnt/PCP activities, through interaction with the Dally-like homolog Knypek.
Caneparo L
,
Huang YL
,
Staudt N
,
Tada M
,
Ahrendt R
,
Kazanskaya O
,
Niehrs C
,
Houart C
.
???displayArticle.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.
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17322405
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Ahn,
Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning.
2004, Pubmed
Ahn,
Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning.
2004,
Pubmed
Axelrod,
Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways.
1998,
Pubmed
,
Xenbase
Belenkaya,
Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis but regulated by the glypican members of heparan sulfate proteoglycans.
2004,
Pubmed
Boutros,
Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling.
1998,
Pubmed
Brembeck,
Balancing cell adhesion and Wnt signaling, the key role of beta-catenin.
2006,
Pubmed
Dorsky,
Two tcf3 genes cooperate to pattern the zebrafish brain.
2003,
Pubmed
Dubrulle,
fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo.
2004,
Pubmed
Erter,
Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo.
2001,
Pubmed
,
Xenbase
Fedi,
Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling.
1999,
Pubmed
Feldman,
Lefty antagonism of Squint is essential for normal gastrulation.
2002,
Pubmed
Galli,
Glypican 4 modulates FGF signalling and regulates dorsoventral forebrain patterning in Xenopus embryos.
2003,
Pubmed
,
Xenbase
Giráldez,
HSPG modification by the secreted enzyme Notum shapes the Wingless morphogen gradient.
2002,
Pubmed
Glinka,
Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction.
1998,
Pubmed
,
Xenbase
Harfe,
Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities.
2004,
Pubmed
Heisenberg,
A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon.
2001,
Pubmed
Heisenberg,
Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation.
2000,
Pubmed
Houart,
A small population of anterior cells patterns the forebrain during zebrafish gastrulation.
1998,
Pubmed
Houart,
Establishment of the telencephalon during gastrulation by local antagonism of Wnt signaling.
2002,
Pubmed
Hsieh,
A new secreted protein that binds to Wnt proteins and inhibits their activities.
1999,
Pubmed
,
Xenbase
Isaac,
FGF and genes encoding transcription factors in early limb specification.
2000,
Pubmed
Kawano,
Secreted antagonists of the Wnt signalling pathway.
2003,
Pubmed
,
Xenbase
Kazanskaya,
The role of Xenopus dickkopf1 in prechordal plate specification and neural patterning.
2000,
Pubmed
,
Xenbase
Kibardin,
Metastasis-associated kinase modulates Wnt signaling to regulate brain patterning and morphogenesis.
2006,
Pubmed
,
Xenbase
Kiecker,
A morphogen gradient of Wnt/beta-catenin signalling regulates anteroposterior neural patterning in Xenopus.
2001,
Pubmed
,
Xenbase
Kiecker,
The role of prechordal mesendoderm in neural patterning.
2001,
Pubmed
Kilian,
The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation.
2003,
Pubmed
Kim,
Repressor activity of Headless/Tcf3 is essential for vertebrate head formation.
2000,
Pubmed
Kim,
Specification of an anterior neuroectoderm patterning by Frizzled8a-mediated Wnt8b signalling during late gastrulation in zebrafish.
2002,
Pubmed
,
Xenbase
Kimura-Yoshida,
Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm.
2005,
Pubmed
Kramer,
Heparan sulfate core proteins in cell-cell signaling.
2003,
Pubmed
,
Xenbase
Kreuger,
Opposing activities of Dally-like glypican at high and low levels of Wingless morphogen activity.
2004,
Pubmed
Kühl,
Antagonistic regulation of convergent extension movements in Xenopus by Wnt/beta-catenin and Wnt/Ca2+ signaling.
2001,
Pubmed
,
Xenbase
Lagutin,
Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development.
2003,
Pubmed
Lekven,
Zebrafish wnt8 encodes two wnt8 proteins on a bicistronic transcript and is required for mesoderm and neurectoderm patterning.
2001,
Pubmed
Leyns,
Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer.
1997,
Pubmed
,
Xenbase
Li,
Cell migration and chick limb development: chemotactic action of FGF-4 and the AER.
1999,
Pubmed
Lin,
Developmental roles of heparan sulfate proteoglycans in Drosophila.
2002,
Pubmed
Macdonald,
Regulatory gene expression boundaries demarcate sites of neuronal differentiation in the embryonic zebrafish forebrain.
1994,
Pubmed
Mao,
LDL-receptor-related protein 6 is a receptor for Dickkopf proteins.
2001,
Pubmed
,
Xenbase
Mao,
Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling.
2002,
Pubmed
Mukhopadhyay,
Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse.
2001,
Pubmed
,
Xenbase
Myers,
Convergence and extension in vertebrate gastrulae: cell movements according to or in search of identity?
2002,
Pubmed
Nasevicius,
Effective targeted gene 'knockdown' in zebrafish.
2000,
Pubmed
Niehrs,
Dickkopf1 and the Spemann-Mangold head organizer.
2001,
Pubmed
,
Xenbase
Piccolo,
The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals.
1999,
Pubmed
,
Xenbase
Richard,
Fibroblast growth factor (FGF)-2 mediates cell attachment through interactions with two FGF receptor-1 isoforms and extracellular matrix or cell-associated heparan sulfate proteoglycans.
2000,
Pubmed
Shinya,
Zebrafish Dkk1, induced by the pre-MBT Wnt signaling, is secreted from the prechordal plate and patterns the anterior neural plate.
2000,
Pubmed
,
Xenbase
Stern,
Initial patterning of the central nervous system: how many organizers?
2001,
Pubmed
Strutt,
Planar polarity is positively regulated by casein kinase Iepsilon in Drosophila.
2006,
Pubmed
Tada,
Non-canonical Wnt signalling and regulation of gastrulation movements.
2002,
Pubmed
,
Xenbase
Tamai,
LDL-receptor-related proteins in Wnt signal transduction.
2000,
Pubmed
,
Xenbase
Tickle,
Vertebrate limb development--the early stages in chick and mouse.
2001,
Pubmed
Topczewski,
The zebrafish glypican knypek controls cell polarity during gastrulation movements of convergent extension.
2001,
Pubmed
Wallingford,
Vertebrate gastrulation: polarity genes control the matrix.
2005,
Pubmed
,
Xenbase
Wang,
Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8.
1997,
Pubmed
,
Xenbase
Willert,
Wnt signaling: is the party in the nucleus?
2006,
Pubmed
Wilson,
Early steps in the development of the forebrain.
2004,
Pubmed
Yamaguchi,
Heads or tails: Wnts and anterior-posterior patterning.
2001,
Pubmed
Zhang,
Membrane heparan sulfate proteoglycan-supported FGF2-FGFR1 signaling: evidence in support of the "cooperative end structures" model.
2001,
Pubmed
del Barco Barrantes,
Dkk1 and noggin cooperate in mammalian head induction.
2003,
Pubmed
,
Xenbase
van Tilbeurgh,
Colipase: structure and interaction with pancreatic lipase.
1999,
Pubmed
