Rosette formations as symmetry-breaking events: theory and experiment

Abstract: Multicellular rosettes are observed in different situations such as morphogenesis, wound healing, and cancer progression. While some molecular insights have been gained to explain the presence of these assemblies of five or more cells around a common center, what are the tunable, global features that favors/hinders their formation is still largely unknown. Here, we made use of a Voronoi dynamical model to investigate the ingredients driving the emergence of rosettes characterized by different degree of stability and organization. We found that (i) breaking the local spatial symmetry of the system, i.e., introducing curvature-inducing defects, allows for the formation of rosette-like structures (ii) whose probability of formation depends on the characteristic of the cellular layer. In particular, a trade-off between tissue fluidity and single cell deformability dictates the assembly of transient rosettes, that are strongly stabilized in the presence of cell alignment interactions. To test our model predictions, we performed fluorescence microscopy experiments on rosette-forming neural populations derived from induced pluripotent stem cells (iPSCs), finding significant agreement. Overall, our work may set the stage to gain an unifying understanding of the plethora of biophysical mechanisms involving the occurrence of rosette-like structure both in physiology and their altered formation in pathology.