Identification and functional characterization of cardiac pacemaker cells in zebrafish

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Evolutionary Biology

Background:

• The cardiac conduction system, responsible for heart rhythm, is well-characterized in mammals but its evolutionary origins in lower vertebrates remain unclear.
• Mammalian sinus node pacemaker cells originate from progenitors expressing T-box transcription factor 3 (Tbx3) and Islet-1 (Isl1).

Purpose of the Study:

• To investigate the evolutionary origin and molecular basis of the cardiac conduction system in zebrafish.
• To identify structural and molecular components of the pacemaker function in a lower vertebrate model.

Main Methods:

• Analysis of zebrafish embryos lacking the LIM/homeodomain-containing transcription factor Isl1.
• 3D reconstruction of gene expression patterns in embryonic and adult zebrafish hearts.
• In vivo labeling and electrophysiological characterization of Isl1-positive cells.

Main Results:

• Zebrafish lacking Isl1 exhibited heart rate defects and pacemaker dysfunction.
• A novel, Isl1-positive and Tbx2b-positive myocardial region was identified at the sinus venosus-atrium junction.
• Isl1-positive cells form a ring-shaped structure with unique pacemaker activity.

Conclusions:

• Isl1-expressing cells organized in a ring structure function as the pacemaker in the adult zebrafish heart.
• This study identifies an evolutionarily conserved component of the cardiac conduction system in a lower vertebrate.
• The findings provide insights into the evolutionary origins of cardiac pacemaking.