Figure 1. The Enhancer Switching Model as a molecular realization of the Speed Regulation Model.

(A) The Speed Regulation Model for periodic patterning. Left: Cells can oscillate between two states mediated by a molecular clock: high (shown in dark blue), and low (shown in light blue). The concentration of the speed regulator (shown in gray) modulates the speed of the molecular clock (i.e. its frequency). Right: A gradient of the speed regulator across a tissue (represented by a row of cells) induces a periodic wave that propagates from the high to the low end of the gradient. (B) The Speed Regulation Model for non-periodic patterning. Same as for the periodic case (A), except the molecular clock is replaced with a genetic cascade that mediates the sequential activation of cellular states (represented by different colors). (C) The Enhancer Switching Model, a molecular realization of the Speed Regulation model, is composed of two gene regulatory networks (GRNs): one dynamic and one static. The dynamic GRN can be either a clock (to mediate periodic patterning) or a genetic cascade (to mediate non-periodic patterning). The static GRN is a multi-stable gene circuit that mediates the stabilization of gene expression patterns. The speed regulator activates the dynamic GRN but represses the static GRN, and so a gradient of the speed regulator (shown in gray) mediates a gradual switch from the dynamic to the static GRN along the gradient. Shown are example realizations of dynamic and static GRNs, where the dynamic GRN represents either a molecular clock or a genetic cascade, depending on the absence or presence of the repressive interaction shown in yellow, respectively. (D) Separate dynamic and static enhancers encode the wiring of each gene (shown here only for the red gene) within the dynamic and static GRNs, respectively.