Novel Cardiac Progenitors for All Components of the Heart Except for the Right Ventricle

Mammalian heart is first recognized as the cardiac crescent at the egg cylinder stage, which had been thought to form all components of the heart. Recently, several lineage-tracing experiments using dye-labeling and mouse genetic technique have demonstrated that another cardiac progenitor population, called the second heart field, contributes to the outflow tract, the right ventricle, and a part of the atria. This finding has provided a great impetus for the understanding of cardiac morphogenesis, but it has also raised additional questions such as the potential existence of unique cardiac progenitors that give rise to the left ventricle and the conduction system. Here, we show that a novel cardiac progenitor population is identified by expression and lineage tracing analysis of the Sfrp5 gene. We found that Sfrp5 gene expression was constantly seen in the venous pole of the forming heart, which is later differentiated into the myocardium of the sinus venosus, a precursor of the sinoatrial node. Descendants of Sfrp5-expressing cells were found to contribute not only to the sinus venosus, but also to the left ventricle, atria, and the outflow tract by lineage-tracing analysis using Sfrp5-Cre and -Ert2Cre mice. These results indicate that Sfrp5-expressing cells could include progenitors for the sinus venosus, atria, the left ventricle, and the outflow tract, but not in the right ventricle, implying that the origin of the right ventricle essential for pulmonary circulation could be unique from progenitors for other components in mammalian cardiac development. In this session, we would like to discuss a new understanding of cardiac progenitor distribution.