Related Experiment Video
Updated: Mar 22, 2026
Isolation and Characterization of Single Cells from Zebrafish Embryos
Published on: March 12, 2016
CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish
Xiyang Peng1, Guanming Li1, Yuequn Wang1
1The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Background:
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.
Methods And Results:
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.
Conclusion:
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.
Insights
CXXC5 protein is crucial for heart development in zebrafish, regulating cardiac looping through the Tgfβ signaling pathway. This finding highlights CXXC5
Area of Science:
- Molecular Biology
- Developmental Biology
- Cardiovascular Research
Background:
- CXXC-type zinc-finger protein CXXC5 is linked to cardiovascular disease.
- CXXC5 activates both Tgfβ and myocardial differentiation pathways.
- The specific role of CXXC5 in heart development was previously unknown.
Purpose of the Study:
- To investigate the function of CXXC5 in heart development.
- To elucidate the molecular mechanisms by which CXXC5 influences cardiogenesis.
Main Methods:
- Investigated interactions between zebrafish CXXC5 and SMAD proteins.
- Assessed Tgfβ signaling pathway activity via luciferase reporter assays.
- Analyzed CXXC5 expression patterns during zebrafish cardiogenesis.
- Utilized morpholino-mediated knockdown of cxxc5 to observe developmental defects.
- Examined the rescue effect of hand2 mRNA co-injection.
Main Results:
- CXXC5 interacts with SMAD proteins.
- CXXC5 enhances Tgfβ signaling pathway activity in cardiomyocytes.
- cxxc5 is expressed throughout zebrafish cardiogenesis.
- cxxc5 knockdown leads to cardiac looping defects, dysplasia, and reduced contractility.
- Cardiac development defects in cxxc5 knockdown embryos are associated with downregulated Tgfβ target genes (nkx2.5, hand2, has2).
- Co-injection of hand2 mRNA rescues cardiac looping defects in cxxc5 morphants.
Conclusions:
- This study provides the first in vivo evidence of CXXC5 regulating heart development and cardiac looping via the Tgfβ signaling pathway.
- CXXC5 may serve as a potential diagnostic and prognostic marker for congenital heart disease in fetuses.
More Related Videos
06:51Light-sheet Fluorescence Microscopy to Capture 4-Dimensional Images of the Effects of Modulating Shear Stress on the Developing Zebrafish Heart
Published on: August 10, 2018
04:13Author Spotlight: Understanding Mechanical Forces Involved in Shaping the Zebrafish Heart
Published on: January 3, 2025
