Control of tissue homeostasis, tumorigenesis, and degeneration by coupled bidirectional bistable switches
Fig 4
The coupled bidirectional bistable switches are robust to parameter variation.
(A-B) Parameter sensitivity analysis was performed for the transition thresholds SN2 and SN3 (A) and SN1 and SN4 (B) by individually increasing and decreasing each parameter by 15% and plotting the fold change. Par- and Par+ represent the increase or decrease of parameters, respectively. Par0 represents the set of standard parameter. The diamond shaped-marker shows the thresholds under the standard parameter set. (C) The circular bar plots show the percent changes in the thresholds when each of the parameters is increased or decreased by 15%. The red outline on the bars denotes an increase of 15% in the parameters, while the blue outline denotes a decrease of 15% in the parameters. The solid black circle represents a 0% change. The dotted black circles going outward and inward represent an increase and decrease of 25% change, respectively. (D-E) Two-parameter bifurcation analyses show the dependence of normalized thresholds for activation of tissue degeneration and tumorigenesis on the strength of (D) the YAP/TAZ-SIRT1 feedback loop (kS2), and (E) YAP/TAZ-NOTCH feedback loop (kN2). Par: Parameter.