Abstract
Enteric glia are a fascinating population of cells. Initially identified in the gut wall as the “support” cells of the enteric nervous system, studies over the past 20 years have unveiled a vast array of functions carried out by enteric glia. They mediate enteric nervous system signalling and play a vital role in the local regulation of gut functions. Enteric glial cells interact with other gastrointestinal cell types such as those of the epithelium and immune system to preserve homeostasis, and are perceptive to luminal content. Their functional versatility and phenotypic heterogeneity are mirrored by an extensive level of plasticity, illustrated by their reactivity in conditions associated with enteric nervous system dysfunction and disease. As one of the hallmarks of their plasticity and extending their operative relationship with enteric neurons, enteric glia also display neurogenic potential. In this review, we focus on the development of enteric glial cells, and the mechanisms behind their heterogeneity in the adult gut. In addition, we discuss what is currently known about the role of enteric glia as neural precursors in the enteric nervous system.
Highlights
The enteric nervous system (ENS) is a network of neurons and glial cells located within the wall of the gut that is crucial for control of gastrointestinal function
One possibility is that the enteric glial cells identified by McCallum et al do not come from the vagal neural crest, but rather migrate into the gut as Schwann cell precursors after 5dpf, as identified by El-Nachef and Bronner
This model is likely to take place in differentiating enteric neural crest-derived cells” (ENCCs), and Sox10 expression levels could provide a means to discriminate between enteric glial cells with or without neurogenic potential
Summary
The enteric nervous system (ENS) is a network of neurons and glial cells located within the wall of the gut that is crucial for control of gastrointestinal function. Type IV enteric glia are bipolar cells associated with neuronal processes in the circular and longitudinal smooth muscle layers (Vanderwinden et al, 2003; Gulbransen et al, 2012; Boesmans et al, 2015) Since this classification into four enteric glia subtypes mostly stems from studies on the murine ileum and colon, it will be important to investigate how it holds for other gut regions and whether similar enteric glia subtypes are present in other species, including human. How Schwann cell precursors contribute to the constellation of enteric glial cells in homeostatic conditions is unclear Given their transcriptomic similarities and extensive plasticity (Dulac and Le Douarin, 1991; Rao et al, 2015), distinguishing between intestinal glia that arise from different sources is turning out to be a challenge, and might even be irrelevant from the perspective of ENS function. Further investigation of these different developmental directions can provide important information on the gene regulatory pathways governing ENS differentiation
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