Mini-review: Enteric glial cell heterogeneity: Is it all about the niche?

Enteric glial cells represent the enteric population of peripheral neuroglia. According to their 'glial' nature, their principal function is to support enteric neurons in both structural and functional ways. Mounting evidence however demonstrates that enteric glial cells crucially contribute to the majority of enteric nervous system functions, thus acting as pivotal players in the maintenance of gut homeostasis. Various types of enteric glia are present within the gut wall, creating an intricate interaction network with other gastrointestinal cell types. Their distribution throughout the different layers of the gut wall translates in characteristic phenotypes that are tailored to the local tissue requirements of the digestive tract. This heterogeneity is assumed to be mirrored by functional specialization, but the extensive plasticity and versatility of enteric glial cells complicates a one on one phenotype/function definition. Moreover, the relative contribution of niche-specific signals versus lineage determinants for driving enteric glial heterogeneity is still uncertain. In this review we focus on the current understanding of phenotypic and functional enteric glial cell heterogeneity, from a microenvironmental and developmental perspective.