Cell Patterns Emerge from Coupled Chemical and Physical Fields with Cell Proliferation Dynamics: The Arabidopsis thaliana Root as a Study System

Abstract

A central issue in developmental biology is to uncover the mechanisms by which stem cells maintain their capacity to regenerate, yet at the same time produce daughter cells that differentiate and attain their ultimate fate as a functional part of a tissue or an organ. In this paper we propose that, during development, cells within growing organs obtain positional information from a macroscopic physical field that is produced in space while cells are proliferating. This dynamical interaction triggers and responds to chemical and genetic processes that are specific to each biological system. We chose the root apical meristem of Arabidopsis thaliana to develop our dynamical model because this system is well studied at the molecular, genetic and cellular levels and has the key traits of multicellular stem-cell niches. We built a dynamical model that couples fundamental molecular mechanisms of the cell cycle to a tension physical field and to auxin dynamics, both of which are known to play a role in root development. We perform extensive numerical calculations that allow for quantitative comparison with experimental measurements that consider the cellular patterns at the root tip. Our model recovers, as an emergent pattern, the transition from proliferative to transition and elongation domains, characteristic of stem-cell niches in multicellular organisms. In addition, we successfully predict altered cellular patterns that are expected under various applied auxin treatments or modified physical growth conditions. Our modeling platform may be extended to explicitly consider gene regulatory networks or to treat other developmental systems.

Author Summary

The emergence of tumors results from altered cell differentiation and proliferation during organ and tissue development. Understanding how such altered or normal patterns are established is still a challenge. Molecular genetic approaches to understanding pattern formation have searched for key central genetic controllers. However, biological patterns emerge as a consequence of coupled complex genetic and non-genetic sub-systems operating at various spatial and temporal scales and levels of organization. We present a two-dimensional model and simulation benchmark that considers the integrated dynamics of physical and chemical fields that result from cell proliferation. We aim at understanding how the cellular patterns of stem-cell niches emerge. In these, organizer cells with very low rates of proliferation are surrounded by stem cells with slightly higher proliferation rates that transit to a domain of active proliferation and then of elongation and differentiation. We quantified such cellular patterns in the Arabidopsis thaliana root to test our theoretical propositions. The results of our simulations closely mimic observed root cellular patterns, thus providing a proof of principle that coupled physical fields and chemical processes under active cell proliferation give rise to stem-cell patterns. Our framework may be extended to other developmental systems and to consider gene regulatory networks.