Expression and Function of Members of a Divergent Nuclear Receptor Family in Caenorhabditis Elegans

Nuclear receptors (NRs) are a large class of ligand-regulated transcriptional modulators that have been shown to play roles in many developmental processes. The Caenorhabditis elegans genome is predicted to encode a large and divergent family of NR proteins. The functions of most of these genes are unknown. As a first step toward defining their roles, we have initiated an expression and functional survey of a subset of these genes. In this study, we demonstrate expression of 21 of 28 NR genes examined, indicating that a large fraction of the predicted genes likely encode functional gene products. We show that five genes are expressed predominantly in neuronal cells, while others are expressed in multiple cell types. Interestingly, we find that eight genes are expressed exclusively in the lateral hypodermal (seam) cells. These eight genes share a high degree of overall homology and cluster in a neighbor-joining tree derived from sequence analysis of the NRs, suggesting that they arose by gene duplication from a common ancestor. We show that overexpression of each of three members of this subfamily results in similar developmental defects, consistent with a redundant role for these genes in the function of the lateral hypodermal cells.