Apical-driven cell sorting optimised for tissue geometry ensures robust patterning

ABSTRACT Tissue patterning coordinates morphogenesis, cell dynamics and fate specification. Understanding how these processes are coupled to achieve precision despite their inherent variability remains a challenge. Here, we investigate how salt-and-pepper epiblast and primitive endoderm (PrE) cells sort and robustly pattern the inner cell mass (ICM) of mammalian blastocysts. Quantifying cellular dynamics and mechanics together with simulations show a key role for the autonomously acquired apical polarity of mouse PrE cells in coupling cell fate and dynamics in tissue contexts. Specifically, apical polarity forms actin protrusions and is required for Rac1-dependent migration towards the ICM surface, where PrE cells are trapped due to decreased tension at their apical domain, while depositing an extracellular matrix gradient, breaking the tissue-level symmetry and collectively guiding their own migration. Tissue size perturbations and comparison with monkey blastocysts further demonstrate that the fixed proportion of PrE/epiblast cells is optimal and robust to variability in embryo size.