PUBLICATION
The coiled-coil domain containing protein Ccdc136b antagonizes maternal Wnt/β-catenin activity during zebrafish dorsoventral axial patterning
- Authors
- Wei, S., Shang, H., Cao, Y., Wang, Q.
- ID
- ZDB-PUB-160802-6
- Date
- 2016
- Source
- Journal of genetics and genomics = Yi chuan xue bao 43(7): 431-8 (Journal)
- Registered Authors
- Wang, Qiang
- Keywords
- CCDC136, Dorsal-ventral patterning, Wnt signaling, Zebrafish, β-catenin
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Female
- Gene Expression Regulation, Developmental
- Mothers*
- Proteolysis
- Tumor Suppressor Proteins/metabolism*
- Wnt Signaling Pathway*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- beta Catenin/metabolism
- PubMed
- 27477027 Full text @ J. Genet. Genomics
Citation
Wei, S., Shang, H., Cao, Y., Wang, Q. (2016) The coiled-coil domain containing protein Ccdc136b antagonizes maternal Wnt/β-catenin activity during zebrafish dorsoventral axial patterning. Journal of genetics and genomics = Yi chuan xue bao. 43(7):431-8.
Abstract
The coiled-coil domain containing protein CCDC136 is a putative tumor suppressor and significantly down-regulated in gastric and colorectal cancer tissues. However, little is known about its biological functions during vertebrate embryo development. Zebrafish has two CCDC136 orthologs, ccdc136a and ccdc136b, but only ccdc136b is highly expressed during early embryonic development. In this study, we demonstrate that ccdc136b is required for dorsal-ventral axial patterning in zebrafish embryos. ccdc136b morphants display strongly dorsalized phenotypes. Loss- and gain-of-function experiments in zebrafish embryos and mammalian cells show that Ccdc136b is a crucial negative regulator of the Wnt/β-catenin signaling pathway, and plays a critical role in the establishment of the dorsal-ventral axis. We further find that Ccdc136b interacts with APC, promotes the binding affinity of APC with β-catenin and then facilitates the turnover of β-catenin. These results provide the first evidence that CCDC136 regulates zebrafish dorsal-ventral patterning by antagonizing Wnt/β-catenin signal transduction and suggest a potential mechanism underlying its suppressive activity in carcinogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping