Determinants of the Transition Zone Width of Morphogen Readouts

In tissue patterning, cell fate boundaries often form transition zones with mixed or gradual fates rather than sharp demarcations. Traditionally, such zones in morphogen-driven systems were attributed to fluctuations in morphogen concentrations, especially at low molecule numbers. Here, we present experimental data from the mouse neural tube, the precursor of the central nervous system, which challenges this view. Contrary to expectations, we find that the transition zone width (TZW) does not increase with distance from the morphogen source. By combining experiments, theory, and computational modelling, we identify key factors shaping the TZW. Our findings suggest that cellular readout noise, rather than morphogen fluctuations, determine the TZW. The inferred variability in the parameters defining morphogen dynamics and cellular readout remains within previously reported physiological ranges. This discovery adds to earlier findings that morphogen gradients maintain higher-than-expected patterning precision over long distances, offering new insights into the robustness of developmental processes.