Lavalle, N. G. | bioRxiv Science

bioRxiv2024

Local control of cellular proliferation underlies neuromast regeneration in zebrafish

Biological systems are never in equilibrium but maintain stability despite continuous external disturbances. A prime example of this is organ regeneration, where, despite intrinsically stochastic damage, organs are rebuilt through controlled cellular proliferation. In this study, we employ a cell- based computational modelling approach to investigate the proliferative response to 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, 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.

developmental biology↗

bioRxiv2023

Fluctuations in tissue growth portray homeostasis as a critical state and long-time non-Markovian cell proliferation as Markovian

Tissue growth is an emerging phenomenon that results from the cell-level interplay between proliferation and apoptosis, which is crucial during embryonic development, tissue regeneration, as well as in pathological conditions such as cancer. In this theoretical article, we address the problem of stochasticity in tissue growth by first considering a minimal Markovian model of tissue size, quantified as the number of cells in a simulated tissue, subjected to both proliferation and apoptosis. We find two dynamic phases, growth and decay, separated by a critical state representing a homeostatic tissue. Since the main limitation of the Markovian model is its neglect of the cell cycle, we incorporated a refractory period that temporarily prevents proliferation immediately following cell division, as a minimal proxy for the cell cycle, and studied the model in the growth phase. Importantly, we obtained from this last model an effective Markovian rate, which accurately describes general trends of tissue size. This study shows that the dynamics of tissue growth can be theoretically conceptualized as a Markovian process where homeostasis is a critical state flanked by decay and growth phases. Notably, in the growing non-Markovian model, a Markovian-like growth process emerges at large time scales.

biophysics↗