Tissue flow induces cell shape changes during organogenesis

Selected by Sébastien Harlepp and Jacky G.Goetz (@GoetzJacky)

Summary

When moving, organs generate fluid-like drag forces that impact on the morphology of its cellular constituents.

This preprint from the group of Lisa Manning provides an elegant numerical and experimental work addressing how tissue flow, during development, induces cell shape changes. To demonstrate such phenomenon, they focus on the zebrafish Kupffer’s vesicle (KV) and follow its motion experimentally. They use experimental data to feed their numerical model that consists on a combination of a voronoi vertex model and self-propelled particles (which they name the self-propelled voronoi). Using this numerical tool, they show that fluid behavior and dragging forces, caused by the KV motion within the growing tissue, induces cellular reshaping that eventually leads to KV asymmetry.

Bigger picture

This work combines experimental observations and numerical simulation on the cellular motion embedded in tissues. The study reveals and confirms that global cellular movement in a viscoelastic environment shapes morphological changes in cells composing the organ, thus impacting its shape and orientation in tissues.

During development, the relative importance of biomechanics, genetics and cell signaling still needs to be defined. Pioneering work has shown that fluid flow and global cellular movement influence the tissue organization. This complementary numerical study shows that organ-driven fluid forces need to be taken into account during development.

This proof of principle study opens multiple doors for interrogating the underlying physical process driving the tissue arrangement. Past work showed that differential cellular organization during development introduces turbulent flows and subsequent physical stress to cells undergoing morphogenesis. In this study, cellular deformation is caused by the fluid behavior of cellular interactions, which induces asymetry during organogenesis. Altogether, this innovative model adds a new string to the bow aiming to understand morphogenesis and cellular reshaping from a physical point of view. This work emphasizes the importance of mechanical forces that direct positioning and shape of the tissues.

Open questions

As pointed out by the authors, the model is still prone to improvement. Multiple open questions remain.

From the experimental point of view, the next steps should aim at :

– obtaining the rheological parameters for each type of cells involved in the process

– characterizing each cellular and tissular motion during embryogenesis

From the numerical point of view, the next steps should aim at :

– Switching to a 3D model

– documenting a kinetic evolution in the shape, that cannot be obviously explained in the experimental acquisitions

– Establishing more experimental controls on the intracellular interactions and follow this behavior in silico

More general and open questions suggested by this work:

– what is the effect of physical forces modulated by biochemical signals (stress response) that could change cellular stiffness over time ?

– although this model claims that fluid behavior is needed to reorganize cellular distribution, what happens once the tissue is positioned ? Do we switch to jammed or solid behavior?

Tags: flow, model, organogenesis, tissue mechanics, zebrafish embryo

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