An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy.
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The enteroendocrine cell is the cornerstone of gastrointestinal chemosensation. In the intestine and colon, this cell is stimulated by nutrients, tastants that elicit the perception of flavor, and bacterial by-products; and in response, the cell secretes hormones like cholecystokinin and peptide YY--both potent regulators of appetite. The development of transgenic mice with enteroendocrine cells expressing green fluorescent protein has allowed for the elucidation of the apical nutrient sensing mechanisms of the cell. However, the basal secretory aspects of the enteroendocrine cell remain largely unexplored, particularly because a complete account of the enteroendocrine cell ultrastructure does not exist. Today, the fine ultrastructure of a specific cell can be revealed in the third dimension thanks to the invention of serial block face scanning electron microscopy (SBEM). Here, we bridged confocal microscopy with SBEM to identify the enteroendocrine cell of the mouse and study its ultrastructure in the third dimension. The results demonstrated that 73.5% of the peptide-secreting vesicles in the enteroendocrine cell are contained within an axon-like basal process. We called this process a neuropod. This neuropod contains neurofilaments, which are typical structural proteins of axons. Surprisingly, the SBEM data also demonstrated that the enteroendocrine cell neuropod is escorted by enteric glia--the cells that nurture enteric neurons. We extended these structural findings into an in vitro intestinal organoid system, in which the addition of glial derived neurotrophic factors enhanced the development of neuropods in enteroendocrine cells. These findings open a new avenue of exploration in gastrointestinal chemosensation by unveiling an unforeseen physical relationship between enteric glia and enteroendocrine cells.
Cell Surface Extensions
Microscopy, Electron, Scanning
Published Version (Please cite this version)10.1371/journal.pone.0089881
Publication InfoBohórquez, Diego V; Samsa, Leigh A; Roholt, Andrew; Medicetty, Satish; Chandra, Rashmi; & Liddle, Rodger A (2014). An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy. PLoS One, 9(2). pp. e89881. 10.1371/journal.pone.0089881. Retrieved from https://hdl.handle.net/10161/9382.
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Assistant Professor in Medicine
I am a gut-brain neuroscientist. Though my initial studies focused on GI physiology and nutrition, my expertise evolved to include neuroscience following the many personal stories, which have carefully sharpened my career vision along the way. While pursuing a Doctoral degree in Nutrition, a friend shared her struggles with obesity and gastric bypass surgery. Surgery was a last resort but helped to reduced her body weight dramatically and resolved her diabe
Professor of Medicine
Our laboratory has two major research interests:Enteroendocrine Cell Biology Enteroendocrine cells (EECs) are sensory cells of the gut that send signals throughout the body. They have the ability to sense food and nutrients in the lumen of the intestine and secrete hormones into the blood. Our laboratory has had a longstanding interest in two types of EECs that regulate satiety and signal the brain to stop eating. Chole
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