Enteric glial cells were first described at the end of the 19th century, but they attracted more interest from researchers only in the last decades of the 20th. Although, they have a different embryological origin, the enteric GLIA share many characteristics with astrocytes, the main glial cell type of the central nervous system (CNS), such as in their expression of the same markers and in their functions. Here we review the construction of the enteric nervous system (ENS), with a focus on enteric glia, and also the main studies that have revealed the action of enteric glia in different aspects of gastrointestinal tract homeostasis, such as in the intestinal barrier, in communications with neurons, and in their action as progenitor cells. We also discuss recent discoveries about the roles of enteric glia in different disorders that affect the ENS, such as degenerative pathologies including Parkinson's and prion diseases, and in cases of intestinal diseases and injury.

The enteric glia, a neural crest-derived cell type that composes the Enteric Nervous System, is involved in controlling gut functions, including motility, gut permeability, and neuronal communication. Moreover this glial cell could to give rise to new neurons. It is believed that enteric neurons are generated up to 21 days postnatally; however, adult gut cells with glial characteristics can give rise to new enteric neurons under certain conditions. The factors that activate this capability of enteric glia to differentiate into neurons remain unknown. Here, we followed the progress of this neuronal differentiation and investigated this ability by challenging enteric glial cells with different culture conditions. We found that, in vitro, enteric glial cells from the gut of adult and neonate mice have a high capability to acquire neuronal markers and undergoing morphological changes. In a co-culture system with 3T3 fibroblasts, the number of glial cells expressing βIIItubulin decreased after 7 days. The effect of 3T3-conditioned medium on adult cells was not significant, and fewer enteric glial cells from neonate mice began the neurogenic process in this medium. Laminin, an extracellular matrix protein that is highly expressed by the niche of the enteric ganglia, seemed to have a large role in inhibiting the differentiation of enteric glia, at least in cells from the adult gut. Our results suggest that, in an in vitro approach that provides conditions more similar to those of enteric glial cells in vivo, these cells could, to some extent, retain their morphology and marker expression, with their neurogenic potential inhibited. Importantly, laminin seemed to inhibit differentiation of adult enteric glial cells. It is possible that the differentiation of enteric glia into neurons is related to severe changes in the microenvironment, leading to disruption of the basement membrane. In summary, our data indicated that the interaction between the enteric glial cells and their microenvironment molecules significantly affects the control of their behavior and functions.

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