3D viscoelastic drag forces contribute to cell shape changes during organogenesis in the zebrafish embryo

Abstract

The left-right organizer in zebrafish embryos, Kupffers Vesicle (KV), is a simple organ that undergoes programmed asymmetric cell shape changes that are necessary to establish the left-right axis of the embryo. We use simulations and experiments to investigate whether 3D mechanical drag forces generated by the posteriorly-directed motion of the KV through the tailbud tissue are sufficient to drive such shape changes. We develop a fully 3D vertex-like (Voronoi) model for the tissue architecture, and demonstrate that the tissue can generate drag forces and drive cell shape changes. Furthermore, we find that tailbud tissue presents a shear-thinning, viscoelastic behavior consistent with those observed in published experiments. We then perform live imaging experiments and particle image velocimetry analysis to quantify the precise tissue velocity gradients around KV as a function of developmental time. We observe robust velocity gradients around the KV, indicating that mechanical drag forces must be exerted on the KV by the tailbud tissue. We demonstrate that experimentally observed velocity fields are consistent with the viscoelastic response seen in simulations. This work also suggests that 3D viscoelastic drag forces could be a generic mechanism for cell shape change in other biological processes. HighlightsO_LInew physics-based simulation method allows study of dynamic tissue structures in 3D C_LIO_LImovement of an organ through tissue generates viscoelastic drag forces on the organ C_LIO_LIthese drag forces can generate precisely the cell shape changes seen in experiment C_LIO_LIPIV analysis of experimental data matches simulations and probes tissue mechanics C_LI Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY