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Ccd1, a novel protein with a DIX domain, is a positive regulator in the Wnt signaling during zebrafish neural
Kensuke Shiomi1, Hiroshi Uchida, Kazuko Keino-Masu
1Department of Molecular Neurobiology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennoudai, 305-8575, Tsukuba, Ibaraki, Japan.
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.
Insights
Researchers discovered Ccd1, a novel gene regulating Wnt signaling. Ccd1 acts as a positive regulator in zebrafish neural patterning, influencing cell growth and differentiation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Wnt signaling is vital for cell differentiation, polarity, and growth.
- The canonical Wnt pathway involves Dishevelled (Dvl) and beta-catenin, ultimately activating TCF/LEF transcription factors.
- DIX domains are critical for Wnt pathway mediators like Dvl and Axin.
Purpose of the Study:
- To identify and characterize a novel gene involved in Wnt signaling in zebrafish.
- To elucidate the role of Ccd1 in neural patterning and Wnt pathway regulation.
Main Methods:
- Identification of a novel zebrafish gene, Ccd1, containing a DIX domain.
- Analysis of Ccd1's interaction with Dvl and Axin in vitro.
- Overexpression and dominant-negative studies of Ccd1 in zebrafish embryos.
- Assessment of Ccd1's effect on Wnt-mediated phenotypes and gene expression.
Main Results:
- Ccd1 forms complexes with Dvl and Axin, activating TCF-dependent transcription.
- Overexpression of Ccd1 in zebrafish embryos caused posteriorization (reduced eye and forebrain size).
- Ccd1 functions downstream of Wnt receptors and upstream of Axin in the Wnt pathway.
Conclusions:
- Ccd1 is a novel positive regulator of Wnt signaling in zebrafish neural patterning.
- Ccd1 plays a significant role in embryonic development and tissue patterning.
- Understanding Ccd1's function provides new insights into Wnt pathway mechanisms.
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