Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells.

dc.contributor.author

Bohórquez, DV

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Shahid, RA

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Erdmann, A

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Kreger, AM

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Wang, Y

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Calakos, N

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Wang, F

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Liddle, RA

dc.coverage.spatial

United States

dc.date.accessioned

2015-01-15T19:44:27Z

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2015-02

dc.description.abstract

Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory neurons. We used a monosynaptic rabies virus to define the circuit's functional connectivity in vivo and determined that delivery of this neurotropic virus into the colon lumen resulted in the infection of mucosal nerves through enteroendocrine cells. This neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/25555217

dc.identifier

78361

dc.identifier.eissn

1558-8238

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https://hdl.handle.net/10161/9363

dc.language

eng

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The American Society for Clinical Investigation

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J Clin Invest

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10.1172/JCI78361

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Animals

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Cell Communication

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Cells, Cultured

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Coculture Techniques

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Colon

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Enteroendocrine Cells

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Intestine, Small

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Mice

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Neuroepithelial Cells

dc.title

Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells.

dc.type

Journal article

duke.contributor.orcid

Wang, F|0000-0003-2988-0614

duke.contributor.orcid

Liddle, RA|0000-0002-5498-4151

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/25555217

pubs.begin-page

782

pubs.end-page

786

pubs.issue

2

pubs.organisational-group

Basic Science Departments

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Cell Biology

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Clinical Science Departments

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Duke

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Duke Cancer Institute

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Duke Institute for Brain Sciences

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Institutes and Centers

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Institutes and Provost's Academic Units

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Medicine

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Medicine, Gastroenterology

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Neurobiology

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Neurology

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Neurology, Movement Disorders

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School of Medicine

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University Institutes and Centers

pubs.publication-status

Published

pubs.volume

125

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