Cell Signaling and Transcriptional Regulation in the Nematode C. elegans
Date
2015-06-01
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Abstract
This thesis describes three investigations of basic principles in biology using the nematode C. elegans. It is centered on two general features of biology, cell to cell communication and the activation or inactivation of genes within an organ. In the first study, I examined the role of a conserved TGF-β signaling pathway in body size regulation. This signaling pathway is active in three organs of C. elegans; the pharynx, hypodermis and intestine. Previous research had concluded that signaling in the hypodermis was necessary and sufficient to regulate body size of C. elegans. My results demonstrated two key findings that modify the model of body size regulation. One, that this signaling pathway regulates size of the pharyngeal organ and two, that pharyngeal signaling can contribute in a minor way to overall body size regulation. These results suggest that TGF-β signaling in C. elegans could be coordinating growth of many cells. The second and third studies dealt with transcriptional regulation of terminal gene expression within the intestine. A hierarchy of GATA transcription factors work to specify the intestinal precursor during embryogenesis and mediate intestinal differentiation. Once embryogenesis is complete, two GATA factors, ELT-2 and ELT-7 function to regulate expression of terminal intestinal genes. These two factors are present at apparently equal levels in all intestinal cells, yet some intestinal genes are only expressed in a subset of these cells. The second project explored what other transcription factors are restricting expression of the pho-1 gene to the posterior intestine. The results from repeating work of a previous student revealed the novel finding that pho-1 expression is initially found in the anterior intestinal cells, then becomes restricted by the end of the first larval stage. It was confirmed that the heterochronic gene lin-14 is repressing anterior pho-1 expression, but not by a direct mechanism. The final project was an exploration of the intestinal targets of ELT-2 and ELT-7. RNAseq results indicate ELT-2 is the primary regulatory of gene expression in the intestine, with ELT-7 functioning partially redundantly. Furthermore, genes regulated by both factors were found to have more cis-regulatory elements in their promoters. In summary, these projects have furthered understanding of two conserved features of eukaryote biology, TGF-β signaling in growth regulation and GATA transcriptional regulation in the endoderm.
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Genetics
Citation
Dineen, A. (2015). Cell Signaling and Transcriptional Regulation in the Nematode C. elegans (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25234