An active wetting transition times a fate decision in zebrafish embryonic explants

Embryonic tissues tightly orchestrate spatial cell fate gradients (patterning) and complex shape change (morphogenesis) to ensure robust development. How this is achieved through coordinated cellular activity, biochemical signalling, and mechanical feedback is poorly understood. Using zebrafish whole-embryo explants, known as pescoids, we show that the growing tissue undergoes a spontaneous transition from wetting to dewetting dynamics on glass. This transition coincides tightly with the onset of mesoderm differentiation, indicating a coupled mechanical origin between cell fate determination and active tissue mechanics. But early induction of mesendoderm expression using drug perturbations (activin) decouples the two events, with a delayed dewetting transition. To explain these experimental observations, we develop a minimal continuum model of the tissue as an active fluid coupled to a dynamical cell-fate variable. By combining numerical simulations, theory, and experimental data, we identify feedback mechanisms that allow for robust timing of mesoderm onset by integrating dynamic active forces. Our work suggests a new mechanism whereby dynamically patterned forces can robustly guide a cell-fate decision in an early embryonic tissue.