Worms respond to a large number of volatile and water-soluble chemicals using a few defined chemosensory neurons. Each of these neurons responds to only a subset of odorant stimuli. Thus, each chemosensory neuron is uniquely identified by its sensory properties. The sensory profile of a neuron is probably defined by the expression of specific chemosensory receptors and other signalling molecules in each neuron. I am exploring the mechanisms by which the sensory specificity of each chemosensory neuron is defined and regulated. Using a behavioral screen, we identified a gene
odr-7, that encodes a member of the nuclear receptor family of transcriptional regulators (1).
odr-7 is expressed only in the AWA olfactory neurons. In
odr-7 mutants, the AWA neurons develop normally but lack all sensory function. Thus
odr-7 may regulate the expression of signalling molecules that provide AWA with its unique sensory profile. We have recently shown that a target of
odr-7 regulation is the gene
odr-10 (2).
odr-10 encodes a seven transmembrane domain receptor for the volatile odorant diacetyl, sensed by the AWA neurons.
odr-10 mutants fail to respond selectively to diacetyl and the
odr-10 gene product is localized to the sensory cilia of the AWA neurons. Expression of
odr-10 under a heterologous promoter restores responses to diacetyl, but not to other odorants sensed by the AWA neurons. I plan to further examine the regulation of
odr-10 by
odr-7, and identify other genes that may also regulate
odr-10 expression and function. Additionally, I am examining how
odr-7 specifies AWA function, by identifying genes that act upstream and other genes downstream of
odr-7. In addition to
odr-10, several large families of genes encoding putative chemosensory receptors in the worm have been identified (3). Analysis of the expression patterns of some of these genes has shown that these genes are expressed in small subsets of chemosensory neurons. I am using the candidate chemosensory receptor genes as markers to determine how the fates and functions of other chemosensory neurons in the worm are determined. Using genetic screens and behavioral assays, I will identify genes that are required for the development and function of these neurons, as defined by the expression of the appropriate receptor genes. I am also interested in investigating the roles of nuclear receptors in the development of the worm sensory system. Although nuclear receptors have been implicated in pattern formation and tissue differentiation in many organisms, their roles in the development of the worm are largely unknown. I am exploring the possibility that
odr-7-like genes function to specify other sensory cell types in the worm. We have identified several predicted genes that are homologous to
odr-7 in the worm genome sequence database (4). One of these genes,
nhr-22, is expressed in multiple sensory neuron types. I am taking a reverse genetic approach to understand the roles of
nhr-22 and other
odr-7-like genes in the development and function of chemosensory neurons in the worm. 1. Sengupta, P. et al. (1994) Cell 79, pp 971-980. 2. Sengupta, P. et al. (1996) Cell 84, pp 899-909. 3. Troemel, E.R. et al. (1995) Cell 83, pp 207-218. 4. Sulston et al. (1992) Nature 356, pp 37-41; Sulston, J., Coulson, A. & Waterston, R. et al. personal communication.