Glycoconjugates in Olfactory Cell-Cell Interactions

描述（由申请人提供）：该项目的主要目的是增加我们对发育和再生过程中感觉神经元轴突引导的机制的理解。我们最近发现了一个基因，β -3- n -乙酰氨基葡萄糖转移酶（β - 3gnt1），它在嗅上皮的感觉神经元亚群中表达，也在一些颅神经节和背根神经节的感觉神经元中表达。它编码一种酶，这种酶是合成终止于乳胺的聚糖的关键。β - 3gnt1的表达对于嗅神经元的生长和引导到嗅球中的靶标至关重要。初步证据表明，在β 3gnt1基因零突变的小鼠中，轴突引导受到严重干扰。我们将利用气味受体报告小鼠来描述主要嗅觉系统中β - 3gnt1功能突变的丧失。我们还将分离和分析含有乳胺的蛋白质的结构。嗅觉组织含有一种叫做半乳糖凝集素的蛋白质家族成员，这种蛋白质与乳胺结合，并被认为通过这些含乳胺的蛋白质参与粘附和信号传递功能。我们将分析凝集素与表达乳胺的嗅觉蛋白的结合，并研究凝集素敲除小鼠的引导缺陷。此外，我们将分析主要嗅觉系统再生的独特能力，并确定乳胺/凝集素相互作用在这一过程中所起的作用。初步研究表明，β - 3gnt1突变小鼠的表鼻轴突引导也受到干扰，因此我们将利用表鼻受体报告小鼠分析乳胺在表鼻与副嗅球连接发育中的作用。这些研究将揭示在感觉系统发展过程中共享的分子和机制，并进一步深入了解嗅觉感知的分子和细胞生物学，特别是嗅觉功能损伤后的恢复。项目描述：该项目将阐明嗅觉系统发展所需的复杂聚糖的功能。此外，作为自发再生的模型，这些研究可能会拓宽我们对周围神经损伤和神经退行性疾病潜在治疗方法的理解。

DESCRIPTION (provided by applicant): The main objective of this project is to add to our understanding of the mechanisms underlying sensory neuron axon guidance during development and regeneration. We recently discovered a gene, beta-3-N-acetyl-glucosaminyltransferase (beta-3GnT1) that is expressed by subsets of sensory neurons in the olfactory epithelium but also by sensory neurons in some cranial ganglia and in dorsal root ganglia. It encodes an enzyme that is key to the synthesis of glycans that terminate in Lactosamine. Beta-3GnT1 expression is essential for the growth and guidance of olfactory neurons to targets in the olfactory bulb. Preliminary evidence suggests that axon guidance is severely perturbed in mice with a null mutation in their beta3GnT1 gene. We will characterize the loss of function mutations of beta-3GnT1 in the main olfactory system, using odorant receptor reporter mice. We will also isolate and analyze the structure of lactosamine containing proteins. Olfactory tissues contain members of a family of proteins called galectins that bind to Lactosamine and are thought to be involved in adhesive and signaling functions through these Lactosamine-containing proteins. We will analyze the binding of galectins to olfactory proteins that express Lactosamine and study guidance defects in galectin knockout mice. Furthermore we will analyze the unique ability of the main olfactory system to regenerate and to determine the role that Lactosamine/galectin interactions plays in this process. Preliminary studies show that vomeronasal axon guidance is also perturbed in beta-3GnT1 mutant mice, thus we will analyze the role of Lactosamine in development of vomeronasal connections to the accessory olfactory bulb using vomeronasal receptor reporter mice. These studies will shed new light on molecules and mechanisms shared during development of sensory systems and lead to further insights into the molecular and cellular biology of olfactory perception, particularly the recovery of olfactory function following injury.Project Narrative: This project will shed light on the function of a complex glycan that is required for development of the olfactory system. In addition, as a model for spontaneous regeneration, these studies are likely to broaden our understanding of potential treatments for peripheral nerve injury and neurodegenerative disease.