Two fundamental problems of developmental biology are the understanding of cell fate specification, and the integration of broader environmental contexts into developmental programs. While cell fate specification is largely achieved by differential gene expression programs, environmental integration relies on cellular receptors. A predominant mechanism to mediate both processes utilizes nuclear hormone receptors (NHRs). However, it remains unclear how diverse the NHR’s modes of action are in regulating gene expression. This thesis utilizes the development of the C. elegans germ line as a model system to study a novel link that integrates cell fate specification and the nutritional environment. In C. elegans, germ cell fate specification is chiefly controlled by posttranscriptional mechanisms. Furthermore, overall germline development is influenced by the animal’s nutritional status. However, it remains unknown whether germline posttranscriptional control mechanisms and germ cell fate decisions are linked to nutrition, and if so, how this link may operate in molecular terms.
This thesis reports the characterization of the nuclear hormone receptor nhr-114 and its crucial functions for germline development and fertility. Depending on the tissue of expression, nhr-114 regulates overall germline organization, germ cell proliferation and oogenesis. Importantly, all aspects of nhr-114 function are linked to diet. Feeding nhr-114 mutants with a specific E. coli strain, or a tryptophan-supplemented diet significantly reduces germline development defects and sterility. Based on mutant analysis, nhr-114 was found to have overlapping functions with gld-4 cytoplasmic poly(A) polymerase (cytoPAP). This thesis provides evidence that nhr-114 may function in germ cells in a posttranscriptional manner linked to gld-4 cytoPAP. Further evidence shows that NHR-114 interacts with GLD-4 cytoPAP. Together these findings suggest that NHR-114 may control gene expression by transcriptional and posttranscriptional mechanisms in a tissue-specific manner. This thesis proposes that NHR-114 ensures the input of tryptophan to allow germline development; and that this function integrates nutritional information into the germline gene expression programs according to the environment of the worm. Therefore, NHR-114 potentially provides a direct molecular link to how a developmental program is coordinated with the nutritional status of an animal.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:25946 |
| Date | 07 February 2012 |
| Creators | Gracida Canales, Xicotencatl |
| Contributors | Eckmann, Christian, Vollmer, Günter, Jindra, Marek, Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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