The C. elegans chemosensory system provides an excellent opportunity to investigate the development of individual chemosensory neuron subtypes and to understand the regulation of olfactory receptor gene expression at a single cell resolution. To identify genes that may have a role in the development or function of chemosensory neurons, transgenic animals carrying
ceh-36::GFP arrays that were strongly expressed only in the AWC olfactory and ASE gustatory neurons, were used in genetic screens.
ceh-36 encodes a member of the OTX/OTD family of homeodomain proteins and is required for the specification of the AWC and ASE neurons in C. elegans . More than 30 mutants showing altered expression of
ceh-36::GFP were isolated by EMS mutagenesis.
oy85 mutants exhibit ectopic expression of
ceh-36::GFP in the ASI neurons. The ASI chemosensory neurons detect several water-soluble attractants and dauer pheromone and express the
daf-7 /TGFb ligand.
oy85 was found to be allelic to the previously identified gene
unc-3 , which encodes a member of the family of O/E transcription factors. O/E family members have previously been implicated in olfactory gene regulation and olfactory neuron targeting in rodents. By examining the expression of other neuronal markers in
unc-3 mutants, we found that the ASI neurons in
unc-3 mutants fail to express a subset of ASI-specific genes including
daf-7 /TGFb gene and instead ectopically express genes specific to other chemosensory neurons. Ectopically expressed genes include markers of terminal differentiation such as olfactory receptors and neuropeptides. Interestingly, transcription factors known to specify the cell-fates of these chemosensory neurons were not ectopically expressed in the ASI neurons of
unc-3 mutants. Furthermore, we identified several putative UNC-3 binding sites in the promoters of ectopically expressed genes. Deletion of the UNC-3 binding sites in the promoter of the AWA-specific olfactory receptor gene
odr-10 results in ectopic expression in the ASI neurons. These results strongly suggest that UNC-3 represses the expression of non-ASI-specific genes by directly binding their promoters. Therefore, in addition to cell-specific activation of specific cell fates, the identities of chemosensory neurons in C. elegans may also be specified via cell-specific repressive mechanisms. Interestingly, in well-fed
unc-3 mutant adults which have bypassed the dauer stage, ectopic expression began at the L3 larval stage and is maintained thereafter. However,
unc-3 mutant adults that have transiently passed through the dauer stage did not show ectopic expression. This result suggests that differential gene expression in the ASI neurons may serve as a cellular memory of the developmental history of the animal. Currently we are investigating the behavioral consequences for the altered gene expression profile and examining whether gene expression in other sensory neuron types are also differentially affected by developmental history.