Tissue flow induces cell shape changes during organogenesis

Abstract

In embryonic development, programmed cell shape changes are essential for building functional organs, but in many cases the mechanisms that precisely regulate these changes remain unknown. We propose that fluid-like drag forces generated by the motion of an organ through surrounding tissue could generate changes to its structure that are important for its function. To test this hypothesis, we study the zebrafish left-right organizer, Kupffer's vesicle (KV), using experiments and mathematical modeling. During development, monociliated cells that comprise the KV undergo region-specific shape changes along the anterior-posterior axis that are critical for KV function: anterior cells become long and thin, while posterior cells become short and squat. Here, we develop a mathematical vertex-like model for cell shapes, which incorporates both tissue rheology and cell motility, and constrain the model parameters using previously published rheological data for the zebrafish tailbud [Serwane et al.] as well as our own measurements of the KV speed. We find that drag forces due to dynamics of cells surrounding the KV could be sufficient to drive KV cell shape changes during KV development. More broadly, these results suggest that cell shape changes could be driven by dynamic forces not typically considered in models or experiments.

Understanding laterality disorders and the left-right organizer: Insights from zebrafish

“…During KV remodeling stages KV is not static, but rather moves posteriorly in the tailbud of the elongating embryo. Erdemci-Tandogan, et al (Erdemci-Tandogan et al, 2018) determined that KV moves faster than the surrounding tailbud cells during these stages. Mathematical modeling in this study predicts that KV moving through the tailbud tissue creates drag forces on KV that could generate the cell shape changes observed in vivo.…”