On the role of differential adhesion in gangliogenesis in the enteric nervous system

A defining characteristic of the normal development of the enteric nervous system (ENS) is the existence of 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, we infer that the adhesive capacity of neurons is greater than that of ENC cells. Using a discrete mathematical model, we test the hypothesis that local rules governing differential adhesion of neuronal agents and ENC agents will produce clusters which 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.