Presenter(s): Lillian Carroll − Biology
Faculty Mentor(s): Judith Eisen, Kristi Hamilton
Oral Session 4S
Research Area: Natural Science
Funding: OURS Program
Intestinal health depends on the microbial community within the dynamic intestinal environment. The enteric nervous system (ENS) innervates the intestine and modulates the microbial community composition. ENS reduction causes Hirschsprung disease (HSCR), resulting in intestinal dysmotility. Many HSCR patients develop potentially life-threatening intestinal inflammation. HSCR is genetically complex, with multiple HSCR genetic loci. The zebrafish is an excellent model in which to study the relationship between inflammation and genes linked to HSCR. Zebrafish with a mutation in the HSCR gene, sox10, have fewer enteric neurons, increased intestinal epithelial cell proliferation, and develop microbiota-dependent intestinal inflammation. Zebrafish with a mutation in another HSCR gene, ret, also have fewer ENS neurons but do not exhibit increased intestinal inflammation. sox10 acts in neural crest cells that form the ENS and ret acts within ENS cells, thus, I hypothesized that the intestinal phenotype of sox10;ret double mutants would be similar to the phenotype of sox10 mutants. To test this hypothesis, I analyzed the phenotypes of double mutants. I used PCR to identify mutants and quantified inflammation by counting intestinal neutrophils and recently-proliferated intestinal epithelial cells, and by determining the intestinal bacterial abundance. Surprisingly, and contrary to my hypothesis, sox10;ret double mutants did not exhibit increased intestinal inflammation or cell proliferation compared to wild-types. These results prompt me to reconsider the potential interactions
of the mutated genes, which will provide insights into the role of the ENS as a crucial regulator of the intestinal microbial community and its function in the maintenance of intestinal health.