Tissue Flow Induces Cell Shape Changes During Organogenesis

Abstract

In embryonic development, 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.

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

“…For example, during embryonic development, convergence and extension (CE) movements elongate the notochord [31]. This elongation has been observed in our live imaging and suggests that the notochord "pushes" the KV in the posterior direction through the tailbud cells [13]. Another process that may generate forces on the KV is the active movement of KV posterior cells crawling on tailbud cells and "pulling" the entire KV towards the posterior direction [32].…”

“…microfluidics), very low velocities, and/or very high dynamic viscosity, inertial forces can be neglected, which simplifies the problem to Stokes (or creeping) flow. Given that the KV moves at very slow speeds [13] and its dimensions are in the order of micrometers, we expect that ≪ 1 in our simulations and compare our simulations to the analytical solution of Stokes flow around a sphere ( Figure 2).…”

“…Additional details of the model implementation are provided in Appendix B. In previous work by some of us [6,11,13], asymmetry between anterior and posterior cells in the KV was quantified using the anterior-posterior parameter ( ), which is the difference between the length to width ratio ( ) of anterior and posterior cells ( = 56* − 789* ) from a 2D cross section. While defining from a 2D cross section is straightforward, there are several different choices for how to define when one has access to the full 3D shape [6,13], and we find that such measurements are generally less robust.…”

The Shape and Function of Solid Fascias Depend on the Presence of Liquid Fascias

“…The inner ear, an extraordinary precision organ, is morphogenetically stimulated by the quantity of fluids (hydrostatic pressure) present during embryogenesis; the same pressure manages the quantity of fluids that can intervene [22]. The fluids manage themselves through pressure feedback and, at the same time, influence the duration of growth and the size of the different tissues [22][23]. The presence of fluids influences the synthesis of chalones (mitotic inhibitors) [22].…”

“…During embryogenesis, fluids also influence substances that manage the size of the tissue or organ, such as insulin, target of rapamycin (TOR) signalling pathways and by the Hippo protein kinase (Hpo) [22]. The accumulation of fluids or morphogenic gradient allows cells to synthesize these substances and create self-control of the growth, shape, and function of tissues and organs or organogenesis [22][23]. The structure, like the various components that make up the cell (proteins, microtubules, contact proteins, and more) respond to fluids (inside and outside the cell); without the constant work of fluids (blood, lymph, interstitial fluids, intra and extracellular fluids) there would be no form or function (Figure 1).…”