HCN4 dynamically marks the first heart field and conduction system precursors.

Area of Science:

• Cardiovascular Research
• Developmental Biology
• Molecular Cardiology

Background:

• Cardiac arrhythmia, a major cause of death, often stems from cardiac conduction system (CCS) abnormalities.
• Identifying specific markers for the first heart field and CCS lineages is crucial for disease modeling and biological pacemaker development.

Purpose of the Study:

• To investigate HCN4 as a marker for the first heart field and CCS precursors.
• To elucidate the contributions of first and second heart lineages to the CCS.

Main Methods:

• Generation of HCN4CreERT2, -nuclear LacZ, and -H2BGFP mouse lines.
• Examination of HCN4 expression via immunostaining and reporter gene expression.
• Lineage tracing using various Cre-driver mouse lines (HCN4CreERT2, Isl1Cre, Nkx2.5Cre, Tbx18Cre) and coimmunostaining with CCS markers.

Main Results:

• HCN4 marks the first heart field at cardiac crescent stages.
• HCN4 expression delineates distinct CCS precursors throughout embryonic development, marking the entire CCS by late fetal stages.
• HCN4 expression was also observed in specific subsets of endothelium during development.

Conclusions:

• HCN4 serves as a valuable marker for the first heart field and CCS development.
• Findings provide insight into the contributions of different heart lineages to the CCS.
• HCN4, combined with other markers, can optimize protocols for generating and isolating specific conduction system precursors.