Cell-cell communication controls the timing of gastruloid symmetry-breaking
Oriola, D.; Torregrosa-Cortes, G.; Arato, K.; Fernandez-Munuera, D.; Hahn, E. M.; Anlas, K.; Garcia-Ojalvo, J.; Trivedi, V.
Show abstract
How cell fate decisions coordinate with tissue-scale morphogenesis remains a major challenge in developmental biology. Gastruloids, three-dimensional aggregates of pluripotent stem cells that self-organise and break symmetry via polarised Brachyury/T expression, 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 collectively, with the pluripotent population delaying differentiation and controlling the timing of symmetry breaking. Mechanical measurements reveal differences in surface tension between T-positive and T-negative tissues, consistent 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.
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