Collective fate decisions and cell rearrangements underlie gastruloid symmetry breaking

How cell fate decisions coordinate with tissue-scale morphogenesis remains a major challenge in developmental biology. Gastruloids, three-dimensional aggregates of pluripo-tent stem cells that self-organise and break symmetry via polarised Brachyury/T expres-sion, provide an ideal system to address this question. By generating gastruloids with defined initial proportions of T-expressing cells we show that fate decisions occur collec-tively, with cell-fate proportions influencing the transition rates. Mechanical measure-ments reveal differences in surface tension between T-positive and T-negative tissues, con-sistent with radial cell sorting. Finally, incorporating fate dynamics and mechanics into a computational model recapitulates the sequential symmetry-breaking events observed in vitro. Our findings identify a mechanochemical mechanism underlying axis formation, and demonstrate how multicellular systems can robustly self-organise without external signalling cues.