The
fax-1 gene 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 uncoordinated locomotion. FAX-1 protein accumulates in the nuclei of eighteen neurons and transiently in two non-neuronal cell types. The neurons that express FAX-1 include 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 receptors, such as
glr-1,
glr-2 and
glr-4 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 receptors are not expressed. These observations support a combinatorial role for
fax-1 and
unc-42 in specifying AVA and AVE identity. However, in four types of neurons,
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 also 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. P> P> In addition to the AVA, AVB, and AVE 'command' interneurons, FAX-1 protein also accumulates in the M4 pharyngeal motorneuron , two pairs of neurons in the head that we tentatively identify as the SIBD and SIBV pairs, the AVK and RIC interneuron pairs, and the DVA neuron. We also observe strong, but transient expression of FAX-1 in the distal tip cells from L2 through L4 and in two bilateral pairs of vulval cells ( VulE or VulF ) during L4. While this expression correlates with the time during which these non-neuronal cell types are migrating or undergoing movements associate with morphogenesis, we have not observed gonadal or vulval defects in
fax-1 mutants. Thus
fax-1 function in these cell types, if any, appears to be redundant with another factor, possibly another nuclear receptor (which could have overlapping DNA-binding activity). P> P>
fax-1 is required for normal axon pathfinding by the AVK interneurons (hence the name f asciculation of ax ons defective), as is
unc-42 . The
unc-42 homeobox gene is also required for normal pathfinding by some or all of the 'command' interneurons. The expression of glr::gfp transgenes in the AVA, AVB, and AVE interneurons of
fax-1 mutants allowed us to evaluate the requirement for
fax-1 in axon pathfinding by these neuron types. In contrast to our results for AVK, axon anatomy appeared grossly normal for the AVA, AVB, and AVE interneurons of
fax-1 mutants. Therefore, while
unc-42 functions in regulating axon pathfinding by AVA, AVB, and/or AVE interneurons,
fax-1 does not. This observation underscores the overlapping contributions to transcriptional regulation of neuron identity by
fax-1 and
unc-42 .