Regulation of Programmed Cell Death During C. Elegans Development

Date of Award

Spring 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Genetics

First Advisor

Hammarlund, Marc

Abstract

Programmed cell death (PCD) is a highly conserved process that removes healthy cells during development. While the apoptotic mechanisms that lead to cell death during PCD are well described, the signaling processes that initiate this pathway are incompletely characterized. In C. elegans, PCD is initiated by transcription of egl-1, but the regulation of egl-1 is not fully understood. I established a system for investigating transcriptional regulation of egl-1 by developing a novel reporter design, Q-loop. Q-loop expands functionality of a previously established Q system by adding a positive feedback loop element that enables the study of transiently transcribed genes, such as egl-1 which is briefly expressed in the embryo. Q-loop can also be used to amplify reporter expression of lowly-expressed genes. To study PCD events in cell death mutant animals, I developed egl-1::Q-loop, a novel fluorescent reporter that indelibly marks cells that express egl-1. Here, I demonstrate that egl-1::Q-loop is a high-fidelity reporter of egl-1 expression making it a powerful tool for identifying novel regulators of egl-1 through forward genetic screening, organism-wide investigation of cell-specific egl-1 regulators, and validation of candidate regulators identified from bioinformatic analysis.

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