Regionalized Sequence of Myocardial Cell Growth and Proliferation Characterizes Early Chamber Formation

Increase in cell size and proliferation of myocytes are key processes in cardiac morphogenesis, yet their regionalization during development of the heart has been described only anecdotally. We have made quantitative reconstructions of embryonic chicken hearts ranging in stage from the fusion of the heart-forming fields to early formation of the chambers. These reconstructions reveal that the early heart tube is recruited from a pool of rapidly proliferating cardiac precursor cells. The proliferation of these small precursor cells ceases as they differentiate into overt cardiomyocytes, producing a slowly proliferating straight heart tube composed of cells increasing in size. The largest cells were found at the ventral side of the heart tube, which corresponds to the site of the forming ventricle, as well as the site where proliferation is reinitiated. The significance of these observations is 2-fold. First, they support a model of early cardiac morphogenesis in 2 stages. Second, they demonstrate that regional increase in size of myocytes contributes significantly to chamber formation.