Abstract

In the embryo, exogenous morphogentic signals guide tissue polarization thereby defining the body axes of the future animal. In the absence of such signals, embryonic stem cell aggregates can still spontaneously polarise in vitro, a process known as symmetry-breaking. How cell fate dynamics control tissue polarisation keeping robust cell proportions is still not understood. By combining experiments and mathematical modelling in mouse embryonic stem cell aggregates, we uncover a positive feedback loop that controls the onset of symmetry-breaking. We find that the expression dynamics of the primitive streak gene Bra/T is critically affected by the initial fraction of Bra/T+ cells and demonstrate that a minimal cell fate model including feedback captures the observed Bra/T dynamics. Our model suggests that primed pluripotent cells inhibit differentiation in the aggregates and that cell-cell signalling controls cell fate proportions. In addition, we identify differences in Bra/T expression between the core and the periphery of the aggregates as an early signature of symmetry-breaking prior to polarisation. Mechanical measurements reveal an increase in viscosity and surface tension upon Bra/T expression. We thus propose differential mechanics as the main driver of spatial symmetry breaking in the aggregates. Our work paves the way to understand how symmetry-breaking emerges in embryo-like structures.