The Enteric Nervous System for Epithelial Researchers: Basic Anatomy, Techniques, and Interactions With the Epithelium

Walsh, Kathleen T.; Zemper, Anne E.

doi:10.1016/j.jcmgh.2019.05.003

Cited by 40 publications

(19 citation statements)

References 82 publications

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“…The current study embarked on adapting and optimizing recent tools developed for brain research to explore the gut environment. To date, broad histological characterization of the ENS has been restricted by the limitations of antibody-based labeling approaches (Walsh and Zemper, 2019). Viral-mediated expression allows for vast infectivity of enteric neurons with a single systemic injection, without the use of transgenic animals, and facilitates histology of large, complex, and dynamic tissues such as the small intestine and colon of mice.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Neuronal Activation Shapes the Microbiome and Alters Gut Physiology

Yoo

Griffiths

Thuy‐Boun

et al. 2021

Preprint

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The enteric nervous system (ENS) integrates cues from the brain and from local signals in the gut to coordinate responses that shape the intestinal milieu. Tools to study, and knowledge of, the ENS lag behind brain research. Herein, we deploy novel recombinant adeno-associated viral (rAAV) vectors with enhanced tropism for the gut to map and activate enteric neurons with spatial and temporal resolution. rAAV-mediated fluorescent labelling coupled with whole-tissue clearing methods in the small intestine and colon of mice enables efficient and thorough characterization of the neuronal architecture of the ENS. We also delivered "designer receptors exclusively activated by designer drugs" (DREADDs) to specifically activate gut neurons that express choline acetyltransferase (ChAT+) and tyrosine hydroxylase (TH+). Targeted activation of ChAT+ or TH+ neuronal populations associated with the gastrointestinal (GI) tract altered the intestinal transcriptome of mice, host and microbial proteome, metagenome, and fecal metabolome. We reveal previously unknown and broad roles for neurons in modulating intestinal physiology, mucosal immunity, and gut microbiome structure, and propose novel interactions for the ENS such as regulating fungal colonization and shaping of bile acid profiles. Experimental tools and rich datasets with multi-parameter characterization of the gut ecosystem may enable further study of the ENS.

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Section: Discussionmentioning

confidence: 99%

Peripheral Neuronal Activation Shapes the Microbiome and Alters Gut Physiology

Yoo

Griffiths

Thuy‐Boun

et al. 2021

Preprint

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“…Little is known about ENS development and the specifics of neuronal diversity within proximal GI tract, relative to the intestine and colon ENS (Kaelberer et al ., 2018; Lasrado et al ., 2017; Rakhilin et al ., 2016; Bohorquez et al ., 2015; Walsh and Zemper, 2019; Nagy and Goldstein, 2017; Brookes et al ., 2013). We have observed differences in ENS development between human gastric and intestinal organoids.…”

Section: Discussionmentioning

confidence: 99%

Engineering functional human gastrointestinal organoid tissues using the three primary germ layers separately derived from pluripotent stem cells

Eicher

Kechele

Sundaram

et al. 2021

Preprint

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The development of human organoid model systems has provided new avenues for patient-specific clinical care and disease modeling. However, all organoid systems are missing important cell types that, in the embryo, get incorporated into organ tissues during development. Based on the concept of how embryonic organs are assembled, we developed an organoid assembly approach starting with cells from the three primary germ layers; enteric neuroglial, mesenchymal, and epithelial precursors, all separately derived from human pluripotent stem cells. From these we generated human gastric tissue containing differentiated glands, surrounded by layers of smooth muscle containing functional enteric neurons that controlled contractions of the engineered tissue. We used this highly tractable system to identify essential roles for the enteric nervous system in the growth and regional identity of the gastric epithelium and mesenchyme and for glandular morphogenesis of the antral stomach. This approach of starting with separately-derived germ layer components was applied to building more complex fundic and esophageal tissue, suggesting this as a new paradigm for tissue engineering.

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“…The individual ganglia are connected to each other and to the epithelium by neuronal projections (Nezami and Srinivasan, 2010 ). The ENS, intestinal epithelium, gut microbiota, and immune cells work in harmony together to ensure the proper functioning of the intestine (Walsh and Zemper, 2019 ). ENS-related neurodegeneration is particularly evident in individuals with aging and neurodegenerative disorders.…”

Section: The Effects Of Age Obesity and Diabetes On Neurodegeneratimentioning

confidence: 99%

Role of Sirtuins in Modulating Neurodegeneration of the Enteric Nervous System and Central Nervous System

et al. 2020

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Neurodegeneration of the central and enteric nervous systems is a common feature of aging and aging-related diseases, and is accelerated in individuals with metabolic dysfunction including obesity and diabetes. The molecular mechanisms of neurodegeneration in both the CNS and ENS are overlapping. Sirtuins are an important family of histone deacetylases that are important for genome stability, cellular response to stress, and nutrient and hormone sensing. They are activated by calorie restriction (CR) and by the coenzyme, nicotinamide adenine dinucleotide (NAD+). Sirtuins, specifically the nuclear SIRT1 and mitochondrial SIRT3, have been shown to have predominantly neuroprotective roles in the CNS while the cytoplasmic sirtuin, SIRT2 is largely associated with neurodegeneration. A systematic study of sirtuins in the ENS and their effect on enteric neuronal growth and survival has not been conducted. Recent studies, however, also link sirtuins with important hormones such as leptin, ghrelin, melatonin, and serotonin which influence many important processes including satiety, mood, circadian rhythm, and gut homeostasis. In this review, we address emerging roles of sirtuins in modulating the metabolic challenges from aging, obesity, and diabetes that lead to neurodegeneration in the ENS and CNS. We also highlight a novel role for sirtuins along the microbiota-gut-brain axis in modulating neurodegeneration.

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The Enteric Nervous System for Epithelial Researchers: Basic Anatomy, Techniques, and Interactions With the Epithelium

Cited by 40 publications

References 82 publications

Peripheral Neuronal Activation Shapes the Microbiome and Alters Gut Physiology

Peripheral Neuronal Activation Shapes the Microbiome and Alters Gut Physiology

Engineering functional human gastrointestinal organoid tissues using the three primary germ layers separately derived from pluripotent stem cells

Role of Sirtuins in Modulating Neurodegeneration of the Enteric Nervous System and Central Nervous System

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