Generating Cell Fate Patterns via Mechanical Stress in Stem Cell Colonies*

Embryonic development depends on fate specification events in which a field of initially equivalent cells differentiates in a spatially controlled manner. A key example is neural induction in which a strip of cells differentiates into the neural plate, flanked by the neural plate border (NPB). Classic studies of neural induction have confirmed the role of diffusible chemical signals from neighboring tissues; the role of mechanical signals in fate patterning events like neural induction remains poorly understood.
Recent experiments in stem cell colonies on micropatterned substrates demonstrated that neural induction can be recapitulated without exogenous morphogen gradients [1]. We propose a mechanical model for neural induction in which cell fate determines active contractility and in which mechanical stress biases cell fate. This model reproduces a key experimental observation, that the concentric width of the NPB domain is approximately independent of colony size. The model also predicts a non-monotonic dependence of the NPB domain width on substrate stiffness. Preliminary experimental results are consistent with model predictions.
1. Xue X, Sun Y, et al. Nat Mater. 2018 Jul;17(7):633-641.