PCA Modelling of Multi-species Cell Clusters: Ganglion Development in the Gastrointestinal Nervous System

Abstract

A defining characteristic of the enteric nervous system (ENS) is mesoscale patterned entities called ganglia. Ganglia are clusters of neurons with associated enteric neural crest (ENC) cells, which form in the simultaneously growing gut wall. At first, the precursor ENC cells proliferate and gradually differentiate to produce the enteric neurons; these neurons form clusters with ENC scattered around and later lying on the periphery of neuronal clusters. By immunolabelling neural cell–cell adhesion molecules, the adhesive capacity of neurons is determined to be greater than that of ENC cells. Using a probabilistic cellular automata (PCA) model, we test the hypothesis that local rules governing differential adhesion of neuronal agents and ENC agents will produce clusters that emulate ganglia. The clusters are relatively stable, relatively uniform and small in size, of fairly uniform spacing, with a balance between the number of neuronal and ENC agents. These features are attained in both fixed and growing domains, reproducing, respectively, organotypic in vitro and in vivo observations. Various threshold criteria governing ENC agent proliferation and differentiation and neuronal agent inhibition of differentiation are important for sustaining these characteristics. This investigation suggests possible explanations for observations in normal and abnormal ENS development.