Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart

Hearts of mice lacking IsI1, a LIM homeodomain transcription factor, are completely missing the outflow tract, right ventricle, and much of the atria. isI1 expression and lineage tracing of isI1-expressing progenitors demonstrate that IsI1 is a marker for a distinct population of undifferentiated cardiac progenitors that give rise to the cardiac segments missing in isil mutants. IsI1 function is required for these progenitors to contribute to the heart. In isI1 mutants, isI1-expressing progenitors are progressively reduced in number, and FGF and BMP growth factors are downregulated. Our studies define two sets of cardiogenic precursors, one of which expresses and requires IsI1 and the other of which does not. Our results have implications for the development of specific cardiac lineages, left-right asymmetry, cardiac evolution, and isolation of cardiac progenitor cells.