  In multicellular organisms, epithelial cells form layers separating
compartments responsible for different physiological functions. At the early
stage of epithelial layer formation, each cell of an aggregate defines an inner
and an outer side by breaking the symmetry of its initial state, in a process
known as epithelial polarization. By integrating recent biochemical and
biophysical data with stochastic simulations of the relevant reaction-diffusion
system we provide evidence that epithelial cell polarization is a chemical
phase separation process induced by a local bistability in the signaling
network at the level of the cell membrane. The early symmetry breaking event
triggering phase separation is induced by adhesion-dependent mechanical forces
localized in the point of convergence of cell surfaces when a threshold number
of confluent cells is reached. The generality of the emerging phase separation
scenario is likely common to many processes of cell polarity formation.
