Presenter(s): Lilly Carroll
Faculty Mentor(s): Judith Eisen & Kristi Hamilton
Oral Session 4 S
The enteric nervous system (ENS) innervates the intestine and regulates the dynamic intestinal environment. ENS reduction causes Hirschsprung disease (HSCR), a genetically complex disease that results in intestinal dysmotility and, in many patients, intestinal inflammation. The zebrafish is an excellent model in which to study the relationship between inflammation and genes linked to HSCR. Zebrafish with a mutation in one HSCR gene, sox10, have fewer enteric neurons 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. To investigate the opposing intestinal phenotypes of sox10 and ret mutants, I analyzed intestinal phenotypes of sox10;ret double mutants. Because sox10 acts in neural crest cells that form the ENS and ret acts later, within ENS cells, I hypothesized that intestinal inflammatory phenotypes of sox10;ret double mutants would resemble those of sox10 mutants. To test this hypothesis, I quantified intestinal inflammation in sox10;ret double mutants by counting intestinal neutrophils. Surprisingly, I observed a wild-type (WT) neutrophil abundance phenotype in sox10;ret mutants. This result led me to investigate intestinal enterochromaffin cells, which produce serotonin and express ret but not sox10. I hypothesized that sox10;ret double mutants would exhibit the same decreased enterochromaffin cell phenotype as ret mutants. However, sox10;ret mutants had more enterochromaffin cells that ret mutants and were similar to WT. This result prompts further exploration of the potential interactions of the mutated genes for insights into the role of the ENS in maintenance of intestinal health.