Molecular Inroads into the Anterior Heart Field

In 2001, three research groups described a previously unrecognized population of progenitor cells in pharyngeal mesoderm that gives rise to myocardium at the arterial pole of the heart. In the last 4 years, the major importance of the cellular contribution of pharyngeal mesoderm to normal and pathologic heart development has become apparent. Lineage-tracing experiments have defined the extent to which pharyngeal progenitor cells colonize the heart, revealing a contribution to venous, as well as arterial, pole myocardium; in addition, major molecular inroads have been made into understanding gene regulation in pharyngeal myocardial progenitor cells, implicating forkhead, Gata, LIM homeodomain, MEF2, SMAD, and T-box transcription factors. The key role of the anterior heart field during normal heart development is underscored by the demonstration that both direct and indirect perturbation of myocardial progenitor cells in pharyngeal mesoderm result in congenital heart disease.