The Role of Enteroendocrine Cells on the Development of Enteric Neurons and Smooth Muscle within the Small Intestine

Abstract

By Ololade Akinboyede, Neurobiology; Daniel Kechele, Cincinnati Children's Hospital Medical Center; Heather McCauley, Cincinnati Children's Hospital Medical Center

Advisor: Ilya Vilinsky

Abstract: Enteroendocrine cells (EECs) are rare cells located throughout the gastrointestinal tract. EECs secrete a number of different hormones that help control feeding, nutrient absorption, gut motility, and glucose homeostasis. Lack of EECs or irregular hormone secretion alters the communication between the gut and other organs leading to malnutrition, obesity, and diabetes. How EECs communicate with the brain, either through the circulation and/or direct synaptic connections between the enteric neurons and the vagus nerve, is an active area of research. Considering this gut-brain connection it is unclear whether the development of nerves and muscles will be impacted. We hypothesize that EECs are required for the normal development of enteric neurons and muscle. To address this hypothesis, we are genetically deleting Neurogenin 3 (Neurog3), a transcription factor required for EECs production, in mice and human intestinal organoids thus removing EECs and looking at the effects on these other cell types. We successfully deleted intestinal Neurog3 in mice and human organoids and confirmed the lack of EECs. Immunofluorescence staining of sectioned and whole-mount tissue were assessed for markers of EECs ( Chromogranin A), neurons ( Beta_III Tubulin, Synaptophysin) and muscle (Alpha- Smooth Muscle Actin). Preliminary results suggest that the absence of EECs does not compromise the development and organization of the small intestine in mice and organoids. Ongoing experiments are focusing more on types of enteric neurons present and function.