We are investigating the role of NR genes in the regulation of the C. elegans molting cycle. The C. elegans genome encodes fifteen nuclear receptor (NR) genes that are conserved in sequence in both arthropods and vertebrates. Among these are four NR genes that are orthologs of Drosophila NRs that function in the ecdysone cascade.
nhr-25,
nhr-41, and
nhr-85 are orthologs of Drosophila Ftz-F1, DHR78, and E75, respectively. Initial RNAi and/or GFP expression data implicate these genes in the regulation of nematode molting. Another gene,
nhr-23, (ortholog of Drosophila DHR3), has been shown by others to be required for molting as well (Kostrouchova et al, Development 125: pg. 1617-1626 (1998)).
nhr-25(RNAi) and
nhr-41(RNAi) larvae have defects in shedding molted cuticle.
nhr-25 also functions during embryogenesis and development of the male tail and somatic gonad while the function of
nhr-41 appears to be specific to the molting cycle.
nhr-41(RNAi) larvae display a prolonged lethargus and the molting process can sometimes take many hours to complete. Once animals complete the molt they usually have similar difficulties at the next molt. L1 lethality is also observed in
nhr-41 RNAi experiments and appears to result from a complete block in the molting process. GFP expression data indicates that
nhr-41 is expressed in a variety of cell types while
nhr-25 and
nhr-85 are expressed exclusively in the epidermis and specialized epithelia. We are currently performing a detailed RNAi and gene expression analysis to further dissect the roles of these NRs during the molting cycle.