Presenter: Parham Diba
Mentors: Julia Ganz and Judith Eisen, Biology
Poster: 18
Major: Human Physiology
The enteric nervous system (ENS) is the largest part of the peripheral nervous system, containing about 400–600 million neurons in humans. It comprises a complex network of neurons and glia and controls intestinal functions, such as motility. Hirschsprung disease (HSCR) is a multifactorial congenital disease in which distal intestine is uninnervated and immotile. A variety of signaling pathways, including the endothelin signaling pathway, regulate ENS development during embryonic stages. In mouse, Endothelin3 and endothelin receptor type B regulate ENS development and mutations in these genes are found in some HSCR patients. However, there are still open questions about how the endothelin pathway is involved in ENS development, such as how it affects progenitor migration and neuronal subtype differentiation. To test the role of the endothelin pathway in ENS development, we are generating zebrafish mutants in components of the endothelin pathway using CRISPR/Cas9 genome editing technology. We are currently creating zebrafish mutants in several different endothelin ligands and endothelin converting enzyme 1 and we have generated a mutant in the endothelin receptor gene ednrb1b. We will then analyze the phenotypes of these mutants to learn how ENS progenitor migration and differentiation are affected. Our strategy will enable us to explore the role of endothelin signaling pathway genes in ENS development and to determine if mutations in these genes lead to an HSCR-like phenotype.