The role of tissue mechanics in symmetry breaking during organogenesis in the zebrafish embryo*

The left-right (LR) patterning of internal organs in a vertebrate is vital to its function, and defects in patterning are associated with congenital disease. In the zebrafish embryo, Kupffer’s vesicle (KV) is a transient organ that acts as the LR organizer. As the KV moves through the tailbud, KV cells change shape differently on the anterior and posterior sides of the organ, resulting in an asymmetric distribution of cilia. While such distribution is necessary for establishing LR asymmetry, the upstream changes in cell shape remain poorly understood. Extensive searches for biochemical signaling that may regulate KV architecture have not been fruitful. Here, we take a different approach by analyzing how mechanical drag forces on the KV generated by surrounding tailbud tissue can contribute to asymmetry. We develop a full 3D vertex model of the tissue architecture, instead of the usual 2D models, to better quantify the 3D forces at play. Velocity gradients obtained by particle image velocimetry (PIV) analysis of zebrafish embryos, along with model-based calculations of shear stresses and pressure acting on KV, indicate that tissue-scale mechanical forces are exerted on the KV, and may help drive cell shape changes.