Date of Completion

2023

Thesis Type

College of Arts and Science Honors

Department

Biology

First Advisor

Alicia Ebert

Keywords

Grb2, Zebrafish, Development, Retina, Cell signaling

Abstract

Grb2 or growth factor receptor-bound protein 2 is an adaptor protein involved in the Ras signaling pathway. Adaptor proteins are critical for the development of many tissues and function by tethering upstream signals to downstream molecules to initiate and/or propagate cellular responses (1). Grb2 consists of two functional domains; one binds to phosphorylated tyrosines (the upstream molecule) and the other binds to a proline rich motif, predominately on the guanine nucleotide exchange factor SOS (the downstream molecule) (2). These interactions activate the Ras/MAP Kinase pathway leading to many cellular processes such as division, adhesion, migration, angiogenesis, and vasculogenesis (2, 3, 4, 5).  Most studies address Grb2’s role in the vasculature system or in cell culture, and mice deficient in Grb2 die very early in development, therefore little is known about Grb2’s role in the nervous system (3, 6, 7, 8). A study in mouse cell lines demonstrated Grb2 was necessary in facilitating cortical neuron growth, which displays the importance of Grb2 in development of neural tissues (4).   In this study, we use zebrafish as a model to investigate Grb2’s role in the nervous system. In situ hybridization demonstrates ubiquitous expression of grb2a and grb2b in the zebrafish nervous system. Additionally, loss of Grb2 leads to abnormalities in the peripheral nervous system, and retinal patterning. These studies highlight the varied role for Grb2 in nervous tissue development in zebrafish.

Available for download on Thursday, May 01, 2025

Share

COinS