Physical Mechanisms Create and Loop the Embryonic Heart

Abstract

The morphogenetic mechanisms that drive heart early development are poorly understood. The objective of this study was to determine the role played by physical forces in formation and looping of the heart tube. The work involved integrating experiments on chick embryos with computational models based on the fundamental laws of mechanics.For decades, it was commonly thought that the bilateral heart fields in the early embryo fold directly toward the midline, where they meet and fuse to form the primitive heart tube. Recent studies have challenged this view, however, suggesting that the heart fields fold in a diagonal pattern that carries their cranial aspects toward the midline. Our experiments and models suggest that differential anisotropic growth between mesoderm and endoderm drives diagonal folding to simultaneously create both the heart tube and foregut. Then, contraction along the anterior intestinal portal generates tension that elongates both structures.After the heart tube forms, it begins to loop to create the basic pattern of the mature heart. During the first phase of looping (c‐looping), the heart tube bends and twists into a c‐shaped tube. First, we created cylindrical finite‐element models to simulate the bending process in isolated hearts. With the number of free parameters reduced as much as possible, numerical distributions of mechanical stress and strain were compared to those measured in cultured chick hearts. The results show that published patterns of hypertrophic growth yield results that agree reasonably well with the trends in our data. Next, we extended our model to include realistic 3D geometry and the effects of external loads, including those exerted by the omphalomesenteric veins at the caudal end of the heart tube and splanchnopleuric membrane against the ventral surface. The bending and torsional behaviors of the model are in reasonable agreement with available experimental data from both control and perturbed embryos, suggesting that a combination of differential growth and external loads drives cardiac c‐looping.Support or Funding InformationThis research was supported by NIH grants R01 GM075200, R01 HL083393, and R01 NS070918.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.