Development of the cardiac conduction system in zebrafish

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Genetics

Background:

• The cardiac conduction system (CCS) is crucial for coordinated heartbeats, but its development and function are not fully understood.
• Defects in the CCS can lead to severe arrhythmias and sudden cardiac death.
• Zebrafish are a valuable model organism for studying cardiac development due to genetic tractability and transparent embryos.

Purpose of the Study:

• To develop novel zebrafish models for visualizing and studying the cardiac conduction system (CCS).
• To investigate the impact of altered cardiac function on CCS development.
• To identify genes involved in CCS formation.

Main Methods:

• Transposon-assisted transgenesis was used to create enhancer trap (ET) lines in zebrafish, termed CCS transgenics.
• Fluorescent protein expression marked pacemaker cells in the sino-atrial node (SAN) and atrio-ventricular region (AVR).
• Transposon integration sites were mapped to identify the gene responsible for EGFP expression.

Main Results:

• CCS transgenics displayed fluorescent protein expression in SAN and AVR pacemaker cells from 36 hours post fertilization into adulthood.
• Perturbing cardiac function (e.g., absence of endothelium, altered hemodynamics) led to abnormal SAN compaction in CCS transgenics.
• Transposon mapping identified the gene encoding fibroblast growth factor 2a (fhf2a) as the likely source of EGFP expression.

Conclusions:

• The developed CCS transgenics are effective tools for studying CCS development and function in zebrafish.
• Cardiac function and hemodynamics play a significant role in the proper compaction of the sino-atrial node.
• Fibroblast growth factor 2a (fhf2a) is implicated in cardiac conduction system development.