Functional diversity among the caenorhabditis elegans members of the nuclear receptor superfamily

Abstract

The nuclear receptor superfamily is currently the largest single class of transcriptional regulators. These molecules participate in nearly all areas of biology from developmental programs such as embryogenesis, insect molting, and amphibian metamorphosis to physiological regulation such as thermogensis and cholesterol homeostasis. The nematode, Caenorhabditis elegans, contains more than 260 nuclear receptor genes, 15 of which can be grouped with conserved genes present in phylogenetically distinct animals. Here I report the results of an investigation of the biological function of two C. elegans nuclear receptors. I demonstrate that nhr-2, a diverged member of this superfamily, participates in embryogenesis. nhr-2 is one of the earliest known zygotic genes to be expressed during nematode development. Because of this early expression, an nhr-2 reporter transgene is a valuable tool for the investigation of the components necessary for the onset of zygotic gene expression. I have utilized this reporter to probe the function of a gene necessary for the onset of C. elegans zygotic gene expression. The second gene, nhr-8, is related to the vertebrate vitamin D, pregnane X, and constitutive androstane receptors. I show that this gene enables C. elegans to cope with ingested xenobiotics. A mutation in nhr-8 renders mutant animals more susceptible to the plant toxins colchicine and chloroquine. Consistent with the NHR-8 requirement for ingested xenobiotic resistance, I show that an nhr-8