![]() ![]() We also address how genetic lineage tracing and in vivo imaging approaches in mice have demonstrated unprecedented levels of adult enteric neurogenesis that are required to maintain ENS homeostasis in the face of continual neuronal loss. Here we focus on reviewing the latest work, particularly how the zebrafish model system has been leveraged to understand links between the CNS and ENS in human neurodevelopment. A thorough description of ENS development is beyond the scope of this review but has been covered previously ( Lake and Heuckeroth, 2013 Rao and Gershon, 2018). Recent advances using new model systems and genetic tools are dramatically changing the understanding of ENS development. The ENS exhibits a columnar topology along the radial axis of the gut ( Lasrado et al., 2017), similar to the CNS however, the logic underlying why certain enteric neurons are grouped into ganglia is largely unclear. #NERVOUS SYSTEM STAMP FULL#Nevertheless, the full extent of enteric neuronal heterogeneity and circuitry remain incompletely understood. The ENS contains a diversity of neurons and glia ( Zeisel et al., 2018), and virtually every CNS neurotransmitter is also found in the ENS ( Furness, 2006). There are estimated to be 100 million neurons in the human small intestine alone, making the ENS the largest collection of neurons and glia outside the brain, and by far the largest division of the peripheral nervous system ( Furness, 2006). The submucosal plexus is located in the submucosa, closer to the intestinal lumen, and extends from the stomach through the rectum. The myenteric plexus, which is the larger of the two plexuses, is located between two layers of smooth muscle and extends throughout the digestive tract. The ENS is derived from neural crest progenitors that colonize the gut during fetal development to form two interconnected ganglionated plexuses that wrap around and integrate into the laminar structure of the digestive tract ( Fig. It contains its own intrinsic enteric nervous system (ENS) that regulates a variety of gastrointestinal functions and communicates bidirectionally with the CNS and extraenteric peripheral nervous system. The gut is the largest microbial, endocrine, and immune organ in both humans and mice. ![]() ![]() We conclude by highlighting recent work on muscularis macrophages, a group of immune cells that closely interact with the ENS in the gut wall, and the importance of neurological–immune system communication in digestive health and disease. We discuss major advances in the understanding of enteric glia, and the functional interactions among enteric neurons, glia, and enteroendocrine cells, a large class of sensory epithelial cells. Here, we provide an overview of ENS development and maintenance, and focus on the latest insights gained from the use of novel model systems and live-imaging techniques. Recent advances have elucidated the dynamic nature of the mature ENS, as well as the complex, bidirectional interactions among enteric neurons, glia, and the many other cell types that are important for mediating gut behaviors. ![]() The enteric nervous system (ENS) is a large, complex division of the peripheral nervous system that regulates many digestive, immune, hormonal, and metabolic functions. ![]()
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