Dauer larva formation in C. elegans is a life-history polyphenism that relies on the function of several pathways, including insulin, TGFβ and nuclear hormone receptor signaling. The downstream effectors of these pathways, DAF-16/FOXO, DAF-3/Co-Smad and DAF-12/VDR, are transcription factors (DAF TFs) with broad or ubiquitous expression patterns, null mutations in which result in the inability to form dauers regardless of environmental conditions. In preparation for the dauer diapause, all tissues of the worm undergo extensive morphological and functional remodeling in a coordinated manner. The broad goal of my thesis is to understand how these transcription factors act in different tissues of the worm to regulate the dauer-specific tissue remodeling and gene expression changes. In addition to characterizing dynamic expression pattern of chemosensory GPCR genes in dauer, which revealed an additional layer of plasticity and provided novel entry points to studying remodeling in distinct neuron classes and non- neuronal tissues, I have developed molecular tools – conditional alleles of the daf TFs – that allowed me to address the question of tissue-specificity and cell-autonomy of the DAF TFs in a previously inapproachable way. I have found that DAF TFs act in both cell-autonomous (DAF-16 in neurons, intestine, pharynx) and non-autonomous manner (DAF-16 in the pharynx) to control dauer tissue remodeling. Unlike DAF-16 and DAF-12, the function of DAF-3 in the dauer decision appears to be largely determined by its action in neurons, and specifically in sensory neurons. The three TFs also differ in their roles in pharynx remodeling: while DAF-16 controls dauer pharyngeal morphology and activity both cell-autonomously and non- autonomously, DAF-12 or DAF-3 depletion from pharyngeal muscle does not affect the dauer pharyngeal phenotypes. Yet, all three TFs are required continuously throughout all tissues to maintain the dauer state, once the decision to enter dauer has been made. This work is a first attempt to characterize tissue-specific roles of all transcriptional effectors of the dauer pathways in a systematic way, and contributes to a fundamental understanding of a polyphenic developmental switch regulated by highly conserved molecular pathways.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/d8-1bk7-1k33 |
| Date | January 2019 |
| Creators | Aghayeva, Ulkar |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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