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ZFIN ID: ZDB-PUB-030114-1
Ccd1, a novel protein with a DIX domain, is a positive regulator in the Wnt signaling during zebrafish neural patterning
Shiomi, K., Uchida, H., Keino-Masu, K., and Masu, M.
Date: 2003
Source: Current biology : CB 13(1): 73-77 (Journal)
Registered Authors: Shiomi, Kensuke
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Axin Protein
  • Binding Sites
  • Body Patterning/physiology*
  • Cytoskeletal Proteins
  • DNA-Binding Proteins/metabolism
  • Embryo, Nonmammalian
  • Eye Abnormalities/genetics
  • Eye Proteins
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins/genetics
  • Lymphoid Enhancer-Binding Factor 1
  • Molecular Sequence Data
  • Nervous System/embryology*
  • Nervous System/metabolism
  • Paired Box Transcription Factors
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases/genetics
  • Proteins/genetics
  • Proteins/metabolism*
  • Proto-Oncogene Proteins c-myc/genetics
  • Proto-Oncogene Proteins c-myc/metabolism
  • Repressor Proteins*
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Transcription Factors/metabolism
  • Transfection
  • Wnt Proteins
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
PubMed: 12526749 Full text @ Curr. Biol.
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.