How can tissue shapes and patterns emerge reproducibly and robustly in multicellular systems like animals?  Despite more than 100 years of embryology, it still remains unclear how gene networks, forces and mechanical properties and the metabolic state of the cells integrate together to self-organize complex structures. This is due to our inability to disentangle the combined action of these factors (biophysical properties, gene networks and metabolic activity) within populations of genetically equivalent cells. In our work we focus on understanding the interplay of these factors within the context of the establishment of body axes in metazoans. We take advantage of aggregates of embryonic stem cells (ESCs) that recapitulate hallmarks of early embryonic development in vitro and probe the first symmetry breaking event that establishes anteroposterior polarity in those aggregates. We aim to understand how gene expression controls tissue rheology which can then dictate spatial segregation of cell types, while the metabolic activity of the cells in the background influences signalling and cell fate decisions. In the long term we aspire to generate a theoretical framework that can capture these processes occurring at different time scales and the feedbacks that together generate a robust pattern in multicellular systems. 

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