UC San Diego

Development of the vertebrate heart involves the collaboration between an array of different cell types, each engaging in a meticulously coordinated symphony of spatially and temporally regulated morphogenetic behaviors. Even small errors in cardiac morphogenesis can have severe physiological consequences. In an effort to understand the regulators of cardiac morphogenesis, prior studies have examined the regionalized changes in cell morphology accompany chamber curvature formation. However, we do not yet fully understand the subcellular mechanisms that drive these cell shape changes. Prior studies have also indicated that actomyosin dynamics are important for chamber curvature morphogenesis, and multiple groups have observed differential organization of F-actin in cardiomyocytes of the inner and outer chamber curvatures. Here, we aimed to develop a comprehensive approach to identify distinctions between the actomyosin organization in inner and outer curvature cardiomyocytes that might promote regional changes in cell morphologies. We show that the actomyosin network indeed exhibits differential patterns of organization between cardiomyocytes in the inner and outer ventricular curvatures. We also find that tbx5a mutants, which fail to undergo proper curvature formation, fail to develop curvature-specific patterns of subcellular actomyosin organization. From these data, we propose a model in which the acquisition of regionalized actomyosin organization patterns drives curvature formation by promoting the development of curvature-specific cell morphologies.