Document Type

Honors Project

Publication Date

Spring 6-3-2015

Abstract

Though the pathologies associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s have been known for many years, we still lack a complete understanding of the molecular mechanisms behind these devastating diseases. The nematode Caenorhabditis elegans is a model organism with a simple nervous system that has given biologists a better understanding of the mechanisms of cell division, apoptosis, and other fundamental concepts of cell and molecular biology. Study of the C. elegans RFX transcription factor DAF-19 has helped us better understand the development of the nervous system. Previous research demonstrated that four distinct protein isoforms are encoded for by the daf-19 gene. DAF-19C is an isoform of the transcription factor known to be necessary for cilia development of the sensory neurons of C. elegans. DAF-19M is involved in specification of male-specific sensory neurons. Recent studies have shown that the isoforms DAF-19A and/or DAF-19B function to maintain protein homeostasis at the neuronal synapses. We used extra-chromosomal transgene arrays containing the control regions of one of two target genes fused with GFP to determine if these genes are DAF-19 dependent. We compared expression of these transgenes in WT worms and in worms without functional DAF-19. Additionally, we characterized two novel daf-19a/b isoform-specific variations using RT-PCR and analyzed the expression of the DAF-19 dependent skr-12 transgene in the presence of one of these isoform-specific variations. We found that skr-12, an E3 ligase ortholog potentially involved in ubiquitin-mediated protein degradation, appears to be repressed by DAF-19A/B in non-sensory cells of the nervous system, while expression of asm-3, a gene potentially involved in the degradation of sphingomyelin, is not DAF-19 dependent.

Level of Honors

magna cum laude

Department

Biology

Advisor

Elizabeth De Stasio

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