Degree Type

Dissertation

Date of Award

2019

Degree Name

Doctor of Philosophy

Department

Genetics, Development and Cell Biology

Major

Bioinformatics and Computational Biology

First Advisor

Drena L. Dobbs

Second Advisor

Matthew Hufford

Abstract

The enteric nervous system (ENS) is the set of neurons that control the activity of the gastrointestinal system. These activities include secretion of digestive juices, absorption of food, and motility of the gut. The enteric neurons are derived from the neural crest cells (NCC) which migrate to the gut during development. We have a sparse knowledge of the genes and the signaling pathways that are known to be involved in the migration, specification, and differentiation of the enteric neurons from neural crest precursors. Malfunction in any of these processes hampers normal ENS development and can result in a variety of diseases including Hirschsprung’s disease, a disorder in which the distal intestinal tract lacks enteric neurons. With the aid of transcriptomic study, we aimed to understand the molecular basis behind the different processes of development of a functional enteric nervous system using zebrafish as our model organism.

In my research, we were able to generate the transcriptome of the neuronal cells as well as of the microenvironment that is known to provide external signals to these neurons in a normal developing ENS. We were able to identify previously linked genes and pathways associated with ENS development and also ascertain a large number of novel candidate genes that might be potential regulators in driving a normal ENS development.

We also tried to elucidate the heterogeneity that exists between enteric neurons by performing a single cell transcriptomic study. Our findings from this project provided an insight into the different genetic and molecular factors that are specific to the different developmental stages. Along with shedding a light on the developmental timeline, this project also assisted in unraveling the factors distinctive of the subpopulations of the enteric neurons that reside in the gastrointestinal tract.

Copyright Owner

Sweta Roy-Carson

Language

en

File Format

application/pdf

File Size

159 pages

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