(A-F) show that models of different complexity are able to capture cell cycle oscillations. (A,D) Core components and interactions of the cell cycle oscillator model (CCO) and the FitzHugh-Nagumo oscillator model (FHN), respectively. (B,E) Time series of relaxation oscillations in the CCO and the FHN, respectively. CCO parameters are set on min-1, min-1, nM, and nM/min. For the biological meaning of the parameters, see Appendix 1. FHN parameters are set on and we applied the linear mapping such that the output of both CCO and FHN models are similar. C,F. Phase space projection of the time series of the limit cycle solutions corresponding to (B,E), including nullclines of resp. [cdk1] and . (G) Numerical simulation of the cell cycle oscillator (CCO) model where the Cdc25-related parameters ( and ) are changed in space to define a spatially heterogeneous frequency profile. The left panel shows that the frequency is increased by at the boundary with respect to the cell cycle frequency elsewhere in the domain (see blue shaded region). The right panel illustrates the time series after a transient of ∼ 80 cycles in a domain of size mm. Boundary-driven waves are found to coordinate the whole domain (). (H) Same as A, but now a second internal pacemaker region is introduced (frequency increased by as indicated by orange region). Waves originating at the boundary and at the internal pacemaker region coexist (). (I) Same as B, but with . Mitotic waves are now dominated by the internal pacemaker (). (J) Domain fractions controlled by waves starting from the boundary () and from the internal pacemaker (). is kept constant, while is changed for each simulation using the CCO model. K. Same as J, but for the FitzHugh-Nagumo (FHN) model.