Project R-12789

MicroRNA regulation of enteric glia phenotype and function (Research)

The little brain in our gastrointestinal tract that regulates digestive function, the enteric nervous system, is composed of meticulously wired networks of nerve cells and glia. Enteric glia comprise a heterogeneous population of cells strategically located in all layers of the gut wall. As pivotal regulators of gut function, enteric glial cell phenotype and activity must be tailored to local tissue demands and integrated with the dynamics of surrounding cellular systems. Although our previous studies have shown that the array of enteric glia subtypes appears to be dictated by environmental cues rather than lineage restrictions, the molecular underpinnings for enteric glial cell plasticity and functional specialization are largely unknown. We hypothesize that microRNAs, an important class of posttranscriptional regulators, are crucial determinants of enteric glial cell status during health and disease. In this project, we will define the microRNA profiles associated with alterations in enteric glial identity during gastrointestinal homeostasis and in models of intestinal infection and enteric nervous system injury. We will investigate how particular microRNAs influence enteric glial cell function and how they are dysregulated in human gastrointestinal disorders. The combination of a variety of model systems, novel molecular tools and advanced genetic methodology empower this project to elucidate how microRNAs tweak enteric glial cell characteristics.

01 October 2022 - 30 September 2026