Regulation of Odorant Receptor Gene Expression in Olfactory Sensory Neurons

摘要 嗅觉辨别是通过气味受体（OR）及其受体的化学特异性来实现的。 刻板的嗅觉联系OR是G蛋白偶联受体的一个大亚家族的成员 （GPCR）。小鼠基因组中大约有1000个OR基因。每个嗅觉感觉神经元（OSN） 选择仅表达一个OR，并根据其OR身份将其轴突会聚为刻板的 肾小球目前尚不清楚如何在OSN中进行和维护OR选择。或蛋白质 似乎在OSN特异性中在其OR表达和轴突靶向中起关键作用。本研究的目的 是剖析OR蛋白序列中的调控基序，以确定OR-1的机制。 介导的转录调控。为了进行这项研究，我们建立了一个体外系统， 在其内在细胞环境OSN内有效遗传操纵OR表达。利用该 在体外系统中，在目标1中，我们将检查外源OR表达是否抑制内源OR 以序列特异性方式转录。在目标2中，我们将研究OR表达是否调节 OSN中粘附分子的表达。通过解剖OR序列及其调控功能， 希望能对OR表达选择和OSN轴突导向的机制有更深入的了解。鉴定 OR调节基序将为未来的体内研究奠定基础，并有助于临床设计。 干预措施。

ABSTRACT 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.