Functional analysis of nuclear receptor genes in the nematode Caenorhabditis elegans
Gissendanner, Christopher Ruark
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Nuclear receptors are an important class of transcription factors that regulate a variety of physiological and developmental processes in metazoans. This diversity is also observed in their biochemical function, as nuclear receptors have the capacity to be regulated by endocrine signals as well as through interactions with cell-surface mediated signal transduction pathways. To enhance our understanding of nuclear receptor function, I have performed a functional analysis of selected nuclear receptor genes in the nematode Caenorhabditis elegans. |Caenorhabditis elegans has greater than 270 nuclear receptor genes, as revealed by the completed genome sequence and numerous genetic and molecular studies. Of these 270 nuclear receptor genes, fifteen belong to groups conserved in arthropods and vertebrates. Nine of these fifteen genes are undescribed in their function and expression. As an initial starting point to investigating the nuclear receptor superfamily in C. elegans I analyzed the expression and function of these nine conserved nuclear receptor genes. Using the powerful reverse genetics tool of RNA-mediated interference with gene function, I demonstrated that five of these nine genes have important functions in a variety of biological processes, including gonad development, embryonic and post-embryonic development and tissue morphogenesis. Using transgenic manipulation of C. elegans, I examined the spatial expression patterns of seven genes using green fluorescent protein reporter gene fusions. I found that these seven genes have distinct spatial expression patterns. |Based on these initial data, I selected two genes, nhr-25 and nhr-41, for a more detailed analyses. nhr-25 is the C. elegans ortholog of ftz-f1, one of the more ancient nuclear receptor genes in the Metazoa. nhr-25 has functions during all stages of C. elegans development, specifically in hypodermal and gonadal development, consistent with its spatial expression pattern. nhr-25 and nhr-41 are also required for molting in C. elegans. These two genes, along with a previously described nuclear receptor gene, nhr-23, specifically function in larval development in the molting process. nhr-23 and nhr-25 likely interact with other post-embryonic developmental processes in C. elegans, providing new entry points for investigations into the complex regulation, as well as the evolution, of nematode larval development.