Variability in the timing of a β-catenin pulse biases a stochastic cell fate decision in C. elegans

During development, cell fate decisions are often highly stochastic, but with the frequency of the different possible fates tightly controlled. To understand how signaling networks control the cell fate frequency of such random decisions, we studied the stochastic differentiation of the C. elegans P3.p cell, using time-lapse microscopy to measure the single-cell dynamics of key regulators of cell fate frequency. Strikingly, we observed pulsatile accumulation dynamics of BAR-1/β-catenin, a key component in Wnt signaling, during the cell fate decision. Combining quantitative analysis and mathematical modeling, we found that the timing of the BAR-1/β-catenin pulse was a key determinant of the outcome of the cell fate decision. Our results highlight that timing of cell signaling dynamics, rather than its average level or amplitude, can play an instructive role in determining cell fate.