Local control of cellular proliferation underlies neuromast regeneration in zebrafish

Biological systems are never in equilibrium, yet they maintain stability in the face of continuous external disturbances. A prime example of this is organ regeneration, during which organs are reliably rebuilt through controlled cellular proliferation. In this study, we employ a cell-based computational modelling approach to investigate the proliferative response of an organ after injury. We developed a minimal two-dimensional Cellular Potts Model (CPM) using empirical data from regenerating neuromasts in larval zebrafish. Remarkably, the CPM both qualitatively and quantitatively recapitulates the regenerative response of neuromasts following laser-mediated cell ablation. Assuming that cell proliferation is locally regulated by a delayed switch, we discovered that mitotic activity ceases once the type-dependent number of neighbouring cells exceeds a deterministic critical threshold. An intriguing corollary of our findings is that a local negative feedback loop among identical cells may represent a general mechanism underlying organ-level proportional homeostasis.