The nuclear hormone receptors ( NHR's ) are a class of transcriptional regulators that typically contain a DNA binding domain (DBD) and a ligand binding domain (LBD). Nuclear hormone receptors can be classified based on amino acid sequence relationships in the DBD. Nuclear receptors in the NR2E class, such as tailless ( tll ) in Drosophila , Tlx in mice, PNR in vertebrates and
fax-1 in C. elegans have been found to function in nervous system development. We have been investigating the function of the NR2E nuclear receptors
nhr-67, the C. elegans tailless ortholog , and
nhr-111 , a novel nuclear receptor that is present in C. elegans but not C. briggsae . The DBD's of
fax-1 and
nhr-67 are similar, although evidence from our laboratory suggests that they have different DNA-binding activities (see the abstract by DeMeo et al.) The DBD of
nhr-111 is somewhat diverged, but its LBD is similar to
fax-1 . Our goal is to determine the function and expression pattern of
nhr-67 and
nhr-111 . Deletion of the
nhr-111 gene does not produce an obvious phenotype, whereas deletion of
nhr-67 results in L1 arrest. RNAi analysis of
nhr-67 reveals a postembryonic role in movement, larval growth, molting and vulval morphogenesis. GFP expression studies of
nhr-67 and
nhr-111 argue that both of these genes are expressed in the nervous system and may play a role in nervous system development:
nhr-67: :gfp reporters are expressed in a few pairs of head neurons, while
nhr-111::gfp reporters are expressed in one or two pairs of head neurons and the somatic gonad. We are currently expressing recombinant NHR-67 protein in bacteria in order to produce polyclonal antibodies, which will allow us to determine the expression pattern of endogenous NHR-67 wild-type animals and various mutants by immunofluorescence studies.