A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics

The heart is an organ that pumps blood throughout the body to supply oxygen and to remove carbon dioxide and waste products. Its left and right side are shaped differently to circulate blood through two pathways: to the lungs and to all other organs. As the heart develops inside the embryo, it transforms from a simple, straight tube into a helix shape similar to the shell of a snail. During this process called looping, the helix coils anti-clockwise, which determines where the left and right side of the heart form. It is thought that over 20% of heart anomalies in children may be caused by abnormal looping. Much of what is known about heart development is based on studies in chicken and fish. However, despite its medical significance, it was not fully understood how the heart of mammals acquires its helix shape. Now, Le Garrec et al. were able to investigate the looping process more closely by creating 3D images and computer simulations of the developing mouse heart. First, Le Garrec et al. studied the cells that build the heart and found that left and right cells contribute differently. For example, the number of cells differed between left and right side. The computer simulations then showed that looping is caused by mechanical constraints, which occur because of the way the heart attaches to the body. These mechanical constraints amplify the differences between left and right cells and cause the heart to acquire an oriented helix shape. The computer model could predict how the heart shape will change depending on the type of mechanical constraint, or if cells will have varying levels of left/right differences. The model could also accurately reproduce the shape changes observed in the mouse embryo and predict the abnormal shape of embryos with a genetic defect. The tools generated in this study will help to understand how anomalies could appear as the heart develops in the embryo, and may in the future also be applied to other organs like the gut. A next step will be to explore how genes control the looping of the heart and contribute to heart anomalies in children.