Each olfactory neuron responds to a characteristic subset of odorants. Little is know about the pathways by which specific signaling molecules are expressed in particular olfactory neuron types. C. elegans provides an excellent system in which to investigate how the diversity of the olfactory system is achieved. Mutations in the gene odr-7 were shown to specifically affect the sensory functions of the AWA olfactory neuron type. odr-7 encodes a novel member of the nuclear receptor family, and was shown to regulate the expression of an AWA-specific olfactory receptor.
Our specific aims i n this proposal are three-fold: 1) Identification and characterization of targets of odr-7 regulation in AWA. The goal is to investigate mechanisms of regulation by odr-7, and to identify signaling genes that function downstream of odr-7. An olfactory receptor gene and a gene encoding a channel-like protein were shown to be regulated by odr-7. The molecular mechanisms of regulation of these genes by odr-7 will be explored, and genetic and behavioral screens will be used to identify additional targets of odr-7 regulation. 2) Analysis of the effects of spatial and temporal control of odr-7 expression. The goal is to determine if odr-7 is sufficient for the expression of AWA-like functions. The effect of odr-7 misexpression on gene expression and function of other chemosensory neuron types will be examined. The developmental time period when odr-7 expression is required will be examined using an inducible odr-7 construct. 3) Identification of additional genes required for the determination of sensory specificity of the AWA neurons. The goal is to identify genes that interact with odr-7 to regulate AWA neuron function. Suppressors of a mutation in the putative DNA-binding domain of ODR-7 will be characterized, and yeast two-hybrid analysis will be used to identify genes that function together with odr-7. Nuclear receptor proteins have been implicated in immune responses, development and oncogenesis. Investigation of the mechanisms of odr-7 action, and identification of its targets will yield new insights into the functions of this important class of transcriptional regulators. Our long-term goals are to elucidate the pathways in which odr-7-like genes act in the development and function of sensory neuron types.
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