PUBLICATION
Cfdp1 Is Essential for Cardiac Development and Function
- Authors
- Giardoglou, P., Deloukas, P., Dedoussis, G., Beis, D.
- ID
- ZDB-PUB-230812-44
- Date
- 2023
- Source
- Cells 12(15): (Journal)
- Registered Authors
- Beis, Dimitris
- Keywords
- arrythmias, bradycardia, cardiovascular development, cfdp1, coronary artery disease, zebrafish models of human disease
- MeSH Terms
-
- Animals
- Cardiovascular Diseases*
- Heart
- Humans
- Nuclear Proteins*/metabolism
- Phenotype
- Wnt Signaling Pathway
- Zebrafish*/metabolism
- PubMed
- 37566073 Full text @ Cells
Citation
Giardoglou, P., Deloukas, P., Dedoussis, G., Beis, D. (2023) Cfdp1 Is Essential for Cardiac Development and Function. Cells. 12(15):.
Abstract
Cardiovascular diseases (CVDs) are the prevalent cause of mortality worldwide. A combination of environmental and genetic effectors modulates the risk of developing them. Thus, it is vital to identify candidate genes and elucidate their role in the manifestation of the disease. Large-scale human studies have revealed the implication of Craniofacial Development Protein 1 (CFDP1) in Coronary Artery Disease (CAD). CFDP1 belongs to the evolutionary conserved Bucentaur (BCNT) family, and to date, its function and mechanism of action in Cardiovascular Development are still unclear. We utilized zebrafish to investigate the role of cfdp1 in the developing heart due to the high genomic homology, similarity in heart physiology, and ease of experimental manipulations. We showed that cfdp1 was expressed during development, and we tested two morpholinos and generated a cfdp1 mutant line. The cfdp1-/- embryos developed arrhythmic hearts and exhibited defective cardiac performance, which led to a lethal phenotype. Findings from both knockdown and knockout experiments showed that abrogation of cfdp1 leads to downregulation of Wnt signaling in embryonic hearts during valve development but without affecting Notch activation in this process. The cfdp1 zebrafish mutant line provides a valuable tool for unveiling the novel mechanism of regulating cardiac physiology and function. cfdp1 is essential for cardiac development, a previously unreported phenotype most likely due to early lethality in mice. The detected phenotype of bradycardia and arrhythmias is an observation with potential clinical relevance for humans carrying heterozygous CFDP1 mutations and their risk of developing CAD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping