nhr-23 (CHR3, NF1F4), the homologue of Drosophila DHR3 and mammalian ROR/RZR/RevErbA nuclear hormone receptors, is important for proper epidermal development and molting in C. elegans . Disruption of
nhr-23 function leads to developmental changes including incomplete molting and a short, fat (dumpy) phenotype. Here, we studied the role of
nhr-23 during larval development using expression assays and RNA-mediated interference (RNAi). We show that the levels of expression of
nhr-23 cycle during larval development and that reduction of
nhr-23 function during each intermolt period results in defects at all subsequent molts. Assaying candidate gene expression in populations of animals treated with
nhr-23 RNAi has identified
dpy-7 as a potential gene acting downstream of
nhr-23 . Contrary to that, other collagen genes,
col-12 and
dpy-13 were not affected by
nhr-23 RNAi. We also show that
nhr-25 , which inhibition leads also to a molting defect, is not downstream in
nhr-23 regulatory pathway as is expected from similarity to the Drosophila homologue FTZ-F1. These results define
nhr-23 as a critical regulator of all C. elegans molts and begin to define the molecular pathway for its function.