Abstract
Wnt signaling plays a crucial role in directing cell differentiation, polarity, and growth. In the canonical pathway, Wnt receptors activate Dishevelled (Dvl), which then blocks the degradation of a key signal transducer, beta-catenin, leading to the nuclear accumulation of beta-catenin and induction of Wnt target genes through TCF/LEF family transcription factors. Here we identified a novel zebrafish gene encoding Ccd1, which possesses a DIX (Dishevelled-Axin) domain. DIX domains are essential for the signal transduction of two major Wnt downstream mediators, Dvl and Axin. Ccd1 formed homomeric and heteromeric complexes with Dvl and Axin and activated TCF-dependent transcription in vitro. In addition, overexpression of ccd1 in zebrafish embryos led to a reduction in the size of the eyes and forebrain (posteriorization), as seen with wnt8 overexpression, whereas a dominant-negative ccd1 (DN-ccd1) caused the opposite phenotype. Furthermore, the Wnt activation phenotype induced by ccd1 was inhibited by the expression of axin1 or DN-ccd1, and the wnt8 overexpression phenotype was rescued by DN-ccd1, suggesting that Ccd1 functions downstream of the Wnt receptor and upstream of Axin. These results indicate that Ccd1 is a novel positive regulator in this Wnt signaling pathway during zebrafish neural patterning.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Axin Protein
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Binding Sites
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Body Patterning / physiology*
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Cytoskeletal Proteins
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DNA-Binding Proteins / metabolism
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Embryo, Nonmammalian
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Eye Abnormalities / genetics
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Eye Proteins
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Gene Expression Regulation, Developmental
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Homeodomain Proteins / genetics
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Lymphoid Enhancer-Binding Factor 1
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Molecular Sequence Data
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Nervous System / embryology*
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Nervous System / metabolism
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Protein Serine-Threonine Kinases / genetics
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Protein Structure, Tertiary
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism
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Repressor Proteins*
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Sequence Homology, Amino Acid
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Signal Transduction*
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Transcription Factors / metabolism
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Transfection
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Wnt Proteins
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Zebrafish / embryology*
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Zebrafish / genetics
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Zebrafish Proteins / genetics*
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Zebrafish Proteins / metabolism*
Substances
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AXIN1 protein, human
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Axin Protein
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Eye Proteins
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Homeodomain Proteins
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Lymphoid Enhancer-Binding Factor 1
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PAX6 Transcription Factor
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PAX6 protein, human
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Paired Box Transcription Factors
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Proteins
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Proto-Oncogene Proteins c-myc
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Repressor Proteins
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Transcription Factors
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Wnt Proteins
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Zebrafish Proteins
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dixdc1a protein, zebrafish
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wnt8a protein, zebrafish
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MARK2 protein, human
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Protein Serine-Threonine Kinases