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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21DC010237-01S1
Application #
7873244
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Davis, Barry
Project Start
2009-07-10
Project End
2010-08-31
Budget Start
2009-07-10
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$18,360
Indirect Cost
Name
University of California Davis
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Lee, Wooje; Yun, Jung-Mi; Woods, Rima et al. (2014) MeCP2 regulates activity-dependent transcriptional responses in olfactory sensory neurons. Hum Mol Genet 23:6366-74
Gong, Qizhi (2012) Culture of mouse olfactory sensory neurons. Curr Protoc Neurosci Chapter 3:Unit3.24