Control of tissue homeostasis, tumorigenesis, and degeneration by coupled bidirectional bistable switches
Fig 2
Bifurcation and nullcline analysis displays three states.
(A) The bifurcation diagram shows the steady state of active/unphosphorylated YAP/TAZ as a function of basal expression of unphosphorylated YAP/TAZ (kYTup0). The labeled points SN1, SN2, SN3, and SN4 indicate saddle-node bifurcation points. The black dashed lines represent the unstable steady states while the solid colored lines represent the steady states. The lower blue branch, middle green branch, and upper red branch are defined as the degenerative state, homeostatic state, and tumorigenic state, respectively. The green shaded region shows the monostable range within the homeostatic state, the blue shaded region shows monostable range within the degenerative state, and the red shaded region shows the monostable range within the tumorigenic state. The cyan shaded region shows a bistable region with degenerative and homeostatic states, while the yellow shaded region shows the bistable region with the homeostatic and tumorigenic states. (B) Nullcline analysis of the regulatory system shows the two stable steady states and one unstable steady state when kYTup0 is within the first bistable region (between SN1 and SN2). Example trajectories starting from different initial conditions were shown to represent the dynamics of the system towards the tissue homeostatic and degenerative states. (C) Nullcline analysis of the regulatory system shows the two stable steady states and one unstable steady state when kYTup0 is within the second bistable region (between SN3 and SN4). Example trajectories (black solid lines) starting from different initial conditions were shown to represent the dynamics of the system towards the tissue homeostatic and tumorigenic states.