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Elongations of epithelial colony in vitro: symmetry breaking through collective effects

By Jordi Comelles, SS Soumya, S. Anvitha, Guillaume Salbreux, Frank J├╝licher, Mandar M Inamdar, Daniel Riveline

Posted 04 Sep 2019
bioRxiv DOI: 10.1101/755181

Tissue elongation is a central morphogenetic event occurring in all organisms in development. During this process, symmetry of cells and tissues is broken by different mechanisms, such as neighbor exchange, cell elongation and oriented cell division. While the phenomenon is known to involve remodeling of adherens junctions and acto-myosin at the molecular level, mesoscopic mechanisms leading to distinct morphogenesis processes are poorly understood. This is partly because inputs from morphogen gradients or from neighboring tissues can affect tissue autonomous self-organization in vivo. It is therefore difficult to disentangle cell intrinsic from externally mediated behaviors. Here we use in vitro experiments and numerical simulations to characterize the spontaneous behavior of a growing cell colony in vitro. We show that in vitro tissue elongation arises from anisotropy in the average cell elongation. This anisotropy sets the direction along which boundary cells migrate radially resulting in a non-isotropic elongation that arises primarily through cell elongation. For colonies submitted to a time periodic stretch, the axis of global symmetry breaking can be imposed by external force, and tissue elongation arises through oriented neighbor exchange. Emergence of radially migrating cells and the interplay between cell elongation and cell rearrangements are confirmed by numerical simulations based on a vertex model. Our results suggest that spontaneous shape deformation is related to the mean orientation of the nematic cell elongation field in the absence of any external input. This provides a framework to explain autonomous tissue elongation and how contributions from different mesoscopic mechanisms can be modulated by external forces.

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