Durotaxis bridges phase transition as a function of tissue stiffness in vivo

Physical processes ultimately drive morphogenetic cell movements. Two proposals are that 1) cells migrate toward stiffer tissue (durotaxis) and that 2) the extent of cell rearrangements reflects liquid-solid tissue phase. It is unclear whether and how these concepts are related. Here, we identify fibronectin-dependent tissue stiffness as a control variable that underlies and unifies these phenomena in vivo. In murine limb bud mesoderm, cells are either caged, move directionally by durotaxis or intercalate as a function of their location along a stiffness gradient. A unifying stiffness-phase transition model that is based on a Landau equation accurately predicts cell diffusivity upon loss or gain of fibronectin. Fibronectin is regulated by a WNT5A-YAP positive feedback pathway that controls cell movements, tissue shape and skeletal pattern. The results identify a key determinant of phase transition and show how durotaxis emerges in a mixed phase environment in vivo.