The nuclear receptor (NR) superfamily of transcription factors includes the steroid, thyroid, and retinoid receptors in vertebrates and the ecdysone receptor in insects. The C.elegans genome sequence has revealed 260 NR genes, 5-fold more than is known from any other species. This makes NRs the most abundant transcription factor gene family in the worm. Our recent analysis of the C.elegans NR genes demonstrated that the NR family has undergone extensive diversification in nematodes (Sluder et al (1999) Genome Research 9:103). While most of these NR genes appear to be nematode-specific, 14 belong to conserved NR classes also found in both vertebrates and insects. Members of these conserved classes of NRs should have an important function in the nematode. Seven NRs are currently known to have a function in C.elegans . Of these seven, five are members of conserved classes and two of these five receptors have clear orthologs in vertebrates and insects. We are now investigating the function of the remaining 9 conserved NRs by examining their expression patterns and RNAi phenotypes as well as attempting to correlate them to known genetic loci. We have obtained expression data for all and have documented functions for most of these genes. We have preliminary data correlating two of these genes with known genetic loci (CG & AS abstract). Two of the more intriguing conserved NR genes are
nhr-8 , a member of the PXR/ DHR96 NR class and
nhr-41 , a member of the TR4/ DHR78 NR class.
nhr-8 is required for gut function (TL & AS abstract) and
nhr-41 functions in molting. The role of
nhr-41 in molting is interesting as its insect ortholog, DHR78 , may direct the onset of metamorphosis in insects, upstream of the ecdysone response (Fisk & Thummel (1998) Cell 93:543). Two other C.elegans NR genes,
nhr-23 (Kostrouchova et al (1998) Development 125:1617) and
nhr-25 (CG & AS abstract), also have phenotypes that affect molting and cuticle shedding, respectively. Orthologs of these genes are also involved in molting and metamorphosis in insects, raising the possibility that nematodes and insects share a homologous "molting gene cassette".