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Cfdp1 Is Essential for Cardiac Development and Function
Panagiota Giardoglou1,2, Panos Deloukas3, George Dedoussis2
1Zebrafish Disease Model Laboratory, Center for Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece.
Insights
Craniofacial Development Protein 1 (CFDP1) is essential for heart development. Loss of CFDP1 in zebrafish causes lethal cardiac arrhythmias, revealing its role in cardiovascular health and potential links to coronary artery disease risk.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Genetics
Background:
- Cardiovascular diseases (CVDs) are a leading global cause of death, influenced by genetic and environmental factors.
- Identifying genes like Craniofacial Development Protein 1 (CFDP1) is crucial for understanding CVDs, particularly Coronary Artery Disease (CAD).
- The specific role of CFDP1 in cardiovascular development remains largely unknown.
Purpose of the Study:
- To investigate the function of cfdp1 in embryonic heart development using a zebrafish model.
- To elucidate the molecular mechanisms underlying CFDP1's role in cardiac physiology.
Main Methods:
- Utilized zebrafish for its genomic homology and physiological similarity to humans in cardiac development.
- Employed morpholino knockdown and generated a cfdp1 knockout zebrafish line (cfdp1-/-).
- Analyzed cardiac function, gene expression (Wnt and Notch signaling), and embryonic lethality.
Main Results:
- cfdp1 is expressed during zebrafish embryonic development.
- cfdp1 deficiency resulted in severe cardiac arrhythmias, defective performance, and embryonic lethality.
- Abrogation of cfdp1 led to Wnt signaling downregulation during heart valve development, without impacting Notch signaling.
Conclusions:
- cfdp1 is essential for normal cardiac development and function, with its absence causing early lethality.
- The zebrafish model provides a tool to study CFDP1's role in cardiac physiology.
- Observed bradycardia and arrhythmias in cfdp1 mutants suggest potential clinical relevance for human CAD risk associated with CFDP1 mutations.
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.
