Intestinal Phenotypes of Zebrafish Enteric Nervous System Double Mutants

Simple item page
dc.contributor.authorCarroll, Lillian Alice
dc.date.accessioned2019-11-07T16:08:28Z
dc.date.available2019-11-07T16:08:28Z
dc.date.issued2019
dc.description49 pages
dc.description.abstractThe enteric nervous system (ENS) innervates the intestine and regulates the dynamic intestinal environment. In humans, ENS reduction causes Hirschsprung disease (HSCR), a genetically complex disorder 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 homozygous for a mutation in one HSCR gene, sox10, have fewer enteric neurons and develop microbiota-dependent intestinal inflammation. Zebrafish homozygous for a mutation in another HSCR gene, ret, also have fewer ENS neurons but do not exhibit increased intestinal inflammation. To investigate the opposing intestinal inflammation phenotypes of sox10 and ret mutants, I analyzed intestinal phenotypes of sox10;ret double mutants. Because sox10 acts early in neural crest cells that form the ENS and ret acts later, within ENS cells themselves, 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 and enumerating intestinal bacteria and recently-proliferated intestinal epithelial cells. Surprisingly, I observed a wild-type (WT) neutrophil abundance phenotype in sox10;ret mutants, suggesting that a cell type outside of the ENS is involved in determining the intestinal inflammatory phenotypes of ENS mutants. This result led me to investigate intestinal enterochromaffin cells, which 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 than ret mutants and were similar to WT. This result prompts further exploration of potential interactions between the sox10 and ret genes to gain insights into how these genes interact to regulate intestinal development and the role of the ENS in the maintenance of intestinal health.en_US
dc.identifier.urihttps://hdl.handle.net/1794/25004
dc.language.isoen_US
dc.publisherUniversity of Oregon
dc.rightsCreative Commons BY-NC-ND 4.0-US
dc.subjectBiologyen_US
dc.subjectZebrafishen_US
dc.subjectIntestineen_US
dc.subjectDevelopmenten_US
dc.subjectNervous Systemen_US
dc.subjectSOX10 Geneen_US
dc.titleIntestinal Phenotypes of Zebrafish Enteric Nervous System Double Mutants
dc.typeThesis/Dissertation

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Final_Thesis-Carroll_L.pdf
Size:
1013.12 KB
Format:
Adobe Portable Document Format
Download

Collections

Clark Honors College Theses