Lineage Tree for the Venous Pole of the Heart

RATIONALE: Genetic tracing experiments and cell lineage analyses are complementary approaches that give information about the progenitor cells of a tissue. Approaches based on gene expression have led to conflicting views about the origin of the venous pole of the heart. Whereas the heart forms from 2 sources of progenitor cells, the first and second heart fields, genetic tracing has suggested a distinct origin for caval vein myocardium, from a proposed third heart field. OBJECTIVE: To determine the cell lineage history of the myocardium at the venous pole of the heart. METHODS AND RESULTS: We used retrospective clonal analyses to investigate lineage segregation for myocardium at the venous pole of the mouse heart, independent of gene expression. CONCLUSIONS: Our lineage analysis unequivocally shows that caval vein and atrial myocardium share a common origin and demonstrates a clonal relationship between the pulmonary vein and progenitors of the left venous pole. Clonal characteristics give insight into the development of the veins. Unexpectedly, we found a lineage relationship between the venous pole and part of the arterial pole, which is derived exclusively from the second heart field. Integration of results from genetic tracing into the lineage tree adds a further temporal dimension to this reconstruction of the history of venous myocardium and the arterial pole.