Quantitative Analysis of 3D Tissue Deformation Reveals Key Cellular Mechanism Associated with Initial Heart Looping

Despite extensive study, the morphogenetic mechanisms of heart looping remain controversial because of a lack of information concerning precise tissue-level deformation and the quantitative relationship between tissue and cellular dynamics; this lack of information causes difficulties in evaluating previously proposed models. To overcome these limitations, we perform four-dimensional (4D) high-resolution imaging to reconstruct a tissue deformation map, which reveals that, at the tissue scale, initial heart looping is achieved by left-right (LR) asymmetry in the direction of deformation within the myocardial tube. We further identify F-actin-dependent directional cell rearrangement in the right myocardium as a major contributor to LR asymmetric tissue deformation. Our findings demonstrate that heart looping involves dynamic and intrinsic cellular behaviors within the tubular tissue and provide a significantly different viewpoint from current models that are based on LR asymmetry of growth and/or stress at the tube boundaries. Finally, we propose a minimally sufficient model for initial heart looping that is also supported by mechanical simulations. [Display omitted] •Quantifying tissue and/or cell dynamics is essential for revealing morphogenetic mechanisms•Initial heart looping is achieved by left-right asymmetry in the direction of tissue deformation•The tissue-scale asymmetry is caused by right-specific directional cell rearrangement•The directional cell rearrangement occurs in a F-actin-dependent manner Kawahira et al. reveal that initial heart looping is achieved by left-right (LR) asymmetry in the direction of tissue deformation, originating from right-specific directional cell rearrangement. These findings demonstrate that heart looping involves dynamic/intrinsic cellular behaviors within tubular tissue itself, providing a significantly different viewpoint from previous models focusing on LR asymmetry in growth and/or stress at tube boundaries.