The Cellular and Physical Mechanisms of Developmental Symmetry

The formation and maintenance of bilateral symmetry of the vertebrate body is intimately related to developmental abnormalities such as scoliosis and neural tube defects. The body axis forms in the early embryo when multiple tissues undergo drastic morphogenesis. The mechanical forces and their underlying cellular dynamics that ensure body axis symmetry are poorly understood. I hypothesize that the paraxial mesoderm produces lateral compression on the axis to prevent it from bending. To test this hypothesis, we will image cell and tissue dynamics of body axis formation in chick embryos. Using this information, we will develop biophysical models that predict tissue forces. These models also allow theoretical assessment of the constraints and key parameters that control variability of symmetry. Using surgical ablations and molecular perturbations on different body axis tissues, we will analyze the cellular and tissue mechanisms of asymmetry response and correction. Using a novel device combining high-sensitivity cantilevers coupled with position control and live imaging, we will quantify and alter both forces and mechanical properties of different tissues. Together, these approaches will integrate quantitative maps of cell dynamics, tissue shapes and soft matter mechanics that are essentially a physical solution of body symmetry formation and morphogenesis in general.