Temporal precision of molecular events with regulation and feedback

Cellular events such as cell migration, division, and cell differentiation rely on precise timing. Molecular events inside cells are highly stochastic, and yet cells trigger events with high timing precision. We explore the effect of gene regulatory networks on first passage timing precision. We devise a method to find the global regulation function between the regulator and target gene which optimizes the timing precision. This method can be applied to a range of networks involving two genes such as regulation by an external species combined with autoregulatory feedback on the target gene itself. We confirm that feedback alone is not helpful in increasing timing precision. However, if a regulator is present then the combination of feedback and regulation is more beneficial than regulation alone. Specifically, higher timing precision is achieved by positive feedback when the regulator is high and negative feedback when the regulator is low. Our results are relevant to experimental gene regulatory systems where high timing precision is crucial, such as neuroblast migration during Caenorhabditis elegans development.