Regulation of Odorant Receptor Gene Expression in Olfactory Sensory Neurons

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DESCRIPTION (provided by applicant): Olfactory discrimination is achieved through chemical specificity of odorant receptors (OR) and their stereotypic olfactory connections. ORs are members of a large subfamily of G-protein coupled receptors (GPCR). There are about 1000 OR genes in the mouse genome. Each olfactory sensory neuron (OSN) chooses to express only one OR and converges its axon according to its OR identity to a stereotypic glomerulus. It is not clear how the OR selection is made and maintained within the OSN. OR proteins appear to play critical roles in OSN specificity in its OR expression and axon targeting. The goal of this study is to dissect the regulatory motif within the OR protein sequence in order to define the mechanism of OR- mediated transcription regulation. To carry out this study, we established an in vitro system which allows efficient genetic manipulation of OR expression within its intrinsic cellular environment, the OSN. Utilizing this in vitro system, in Aim 1, we will examine whether exogenous OR expression suppresses endogenous OR transcription in a sequence specific manner. In Aim 2, we will examine whether OR expression regulates adhesion molecule expression in OSNs. Through dissecting OR sequence and their regulatory function, we hope to gain insights into the mechanisms of OR expression choice and OSN axon guidance. Identification of the OR regulatory motif will lay foundations for future in vivo investigations and aid in the design of clinical interventions. PUBLIC HEALTH RELEVANCE: This study aims to understand the regulatory mechanism that controls the identity of olfactory sensory neurons in their odorant receptor choice and their expression of adhesion molecules for axon targeting.