The
fax-1 gene of the nematode C. elegans encodes a conserved nuclear receptor that is the ortholog of the human PNR gene and functions in the specification of neuron identities. Mutations in
fax-1 result in locomotion defects. FAX-1 protein accumulates in the nuclei of 18 neurons, among them the AVA, AVB, and AVE interneuron pairs that coordinate body movements. The identities of AVA and AVE interneurons are defective in
fax-1 mutants; neither neuron expresses the NMDA receptor subunits
nmr-1 and
nmr-2. Other ionotropic glutamate receptor subunits are expressed normally in the AVA and AVE neurons. The
unc-42 homeobox gene also regulates AVA and AVE identity; however,
unc-42 mutants display the complementary phenotype: NMDA receptor subunit expression is normal, but some non-NMDA glutamate receptor subunits are not expressed. These observations support a combinatorial role for
fax-1 and
unc-42 in specifying AVA and AVE identity. However, in four other neuron types,
fax-1 is regulated by
unc-42, and both transcriptional regulators function in the regulation of the
opt-3 gene in the AVE neurons and the
flp-1 and
ncs-1 genes in the AVK neurons. Therefore, while
fax-1 and
unc-42 act in complementary parallel pathways in some cells, they function in overlapping or linear pathways in other cellular contexts, suggesting that combinatorial relationships among transcriptional regulators are complex and cannot be generalized from one neuron type to another.