Editorial introduction for special issue on enteric glia

Abstract

Glia and neurons form a partnership that originates during the early phases of development and inextricably links the two cell types in structure and function. Glia accompany neuron cell bodies and processes throughout the nervous system and act to shape and support nervous system activity. Central nervous system glia have well defined roles in regulating neuron and neural network functions. In contrast, the functions of peripheral glia associated with neurons in internal organs are only recently becoming appreciated. One of the largest populations of peripheral glia resides in the enteric nervous system (ENS) of the digestive tract. The ENS is colloquially referred to as the "second brain" based on its complex intrinsic neurocircuitry that allows it to control basic gastrointestinal functions without input from the brain and spinal cord. A diverse set of enteric glia surround neuronal cell bodies within enteric ganglia and accompany neuronal processes that run within the gut smooth muscle coats and into the mucosa. The field of enteric glial biology has grown considerably in recent years with major advances in understanding the molecular characteristics, phenotypic plasticity and core functions of these cells. Current data show that enteric glia interact with multiple cell types in the gut and regulate homeostasis within the ENS. Enteric glia participate in bi-directional signaling with neurons that functions to modulate ENS activity and subsequently, gut function. These roles are altered during disease and changes to glial phenotype contribute to the pathophysiology of gastrointestinal disorders. However , fundamental questions remain regarding the origin and extent of enteric glial heterogeneity and their interactions with neurons, how enteric glia influence mucosal functions or are influenced by gut microbiota, their neurogenic potential, relationships with immune cells, and roles in gut pathophysiology. Understanding these and other roles of enteric glia in health and disease is required to fully grasp the intricacies of ENS function and will eventually shape whether therapies should consider enteric glia as a therapeutic target or a tool. This Special Issue is intended to provide the reader a concise introduction to several active areas of enteric glial biology research. The mini-reviews summarize topics including intercellular enteric glia-neuron communication, enteric glial heterogeneity, roles of enteric glia in the intestinal epithe-lium and their interactions with gut microbes, enteric glial reactions to inflammation and contributions to inflammatory diseases, roles of enteric glia in tumorigenesis, modeling enteric glial development, and the potential of harnessing enteric glia for therapeutic benefit. Our intent is that these articles will provide the reader, in particular those that are new to the field, with a basic framework to understand current concepts and the state of enteric glia research. Moreover, we hope that this collection will set the stage for the next era of enteric glial biology.