PUBLICATION

CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish

Authors
Peng, X., Li, G., Wang, Y., Zhuang, J., Luo, R., Chen, J., Chen, F., Shi, Y., Li, J., Zhou, Z., Mo, X., Liu, X., Yuan, W., Zeng, Q., Li, Y., Jiang, Z., Wan, Y., Ye, X., Xu, W., Wang, X., Fan, X., Zhu, P., Wu, X., Deng, Y.
ID
ZDB-PUB-160415-8
Date
2016
Source
International Journal of Cardiology   214: 246-253 (Journal)
Registered Authors
Deng, Yun, Wu, Xiushan, Zhu, Ping
Keywords
CXXC5, Cardiogenesis, Congenital heart diseases, Tgfβ signaling pathway
MeSH Terms
  • Animals
  • Binding Sites
  • Cell Line
  • DNA-Binding Proteins/chemistry
  • DNA-Binding Proteins/metabolism*
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins/chemistry
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Myocytes, Cardiac/cytology*
  • Myocytes, Cardiac/metabolism*
  • Protein Binding
  • Rats
  • Signal Transduction
  • Smad Proteins/chemistry
  • Smad Proteins/metabolism*
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/metabolism*
PubMed
27077543 Full text @ Int. J. Cardiol.
Abstract
CXXC-type zinc-finger protein CXXC5 has been reported to be associated with the development of cardiovascular disease. Recently, through signaling pathway screening we found that CXXC5 activated Tgfβ and myocardial differentiation signaling pathways simultaneously. Although the physiological and pathological function of CXXC5 in many organs has been well elucidated, its function in heart remains unclear.
Here, we found that zebrafish CXXC5 and SMAD were interacting through ZF-CXXC and MH1 domain. Over-expression of CXXC5 in cardiomyocyte increased the luciferase report activity of Tgfβ signaling pathway. Spatiotemporal expression profile of cxxc5 showed that it consistently expressed during cardiogenesis. Knockdown of cxxc5 in zebrafish displayed looping defects, cardiac dysplasia, pericardial edema, and decreased contraction ability, accompanied with down-regulation of members referring to cardiac looping downstream genes of Tgfβ signaling pathway, such as nkx2.5, hand2, and has2. Co-injection of hand2 mRNA with cxxc5 morpholino rescued the cardiac looping detects.
Our study is the first to provide an in vivo evidence for cxxc5 regulating heart development and cardiac looping via Tgfβ related signaling pathway. This finding suggested that CXXC5 may serve as a possible marker that has potential diagnostic and prognostic value in fetus with congenital heart disease.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping