Quantitative Analysis of 3D Tissue Deformation Reveals Key Cellular Mechanism Associated with Initial Heart Looping
Naofumi Kawahira, Daisuke Ohtsuka, Naoki Kida, Ken‐ichi Hironaka, Yoshihiro Morishita
Abstract
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.