Impact of Localized Changes to Myosin Activity for Symmetry-Breaking in Zebrafish Embryonic Development

A fundamental question is how organisms control cell and organ morphology during development, and we address this question using Kupffer’s Vesicle (KV), the left-right organizer in zebrafish, as a simple model organ. Both the cells that comprise the KV, and the organ itself, change shape in a stereotyped manner that is important for organ function. While multiple mechanisms have been proposed to govern these shape changes, recent studies combining 3D simulations with laser ablation experiments have shown that the slow movement of KV through the surrounding tailbud tissue generates dynamic forces that alter the organ and cell shape¹. To understand the molecular mechanisms that affect this motion, we have developed an experimental protocol to perturb myosin activity in a localized region of interest in the tailbud, using an optically controlled rho-kinase inhibitor. We predict the impact of such a perturbation using a 3D vertex model with dynamic forces, where pushing forces are applied to KV from the notochord and migratory cells pull the KV from its posterior. We model the effect of the caged rho-kinase inhibitor as a diffusing patch of signal that emanates from a region of interest below the tailbud, which alters both the dynamic forces applied to KV as well as the mechanics of the tailbud tissue. Preliminary results indicate that the patch alters KV motion and influences the cell and organ shape.

¹Manna et al. bioRxiv, https://arxiv.org/pdf/2407.07055