GLYCOCONJUGATES IN CELL-CELL INTERACTIONS

细胞间相互作用中的糖缀合物

• 批准号: 2683912
• 负责人: GERALD A SCHWARTING
• 金额: $ 23.93万
• 依托单位: EUNICE KENNEDY SHRIVER CTR MTL RETARDATN
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2683912
• 关键词: afferent nerve; binding proteins; cell cell interaction; extracellular matrix proteins; gene expression; glycolipids; glycoproteins; immunocytochemistry; immunoelectron microscopy; laboratory mouse; laminin; olfactions; olfactory lobe; olfactory stimulus; polymerase chain reaction; prosencephalon; protein structure function; receptor; receptor binding; receptor expression; tissue /cell culture

DESCRIPTION: The olfactory system of mammals is thought to be capable of distinguishing among thousands of odors. Subtle differences in the molecular structure of some odors can lead to a dramatic change in odor perception. It is now known that the first step in olfactory discrimination involves the interaction of odors with odorant receptors on sensory neurons in the nasal cavity. How the brain determines which receptors have been activated remains a mystery. However, as in most sensory systems, the olfactory system probably uses defined spatial patterns of receptor activation to make connections in the brain. The overall objectives of this proposal are to determine the identity, structure and function of molecules that participate in the spatial organization of connections between the olfactory sensory neurons in the nasal cavity and their axon termination sites in the olfactory bulb. The investigators have proposed three different mechanisms that may be important in the formation of specific olfactory connections, and during the continual neural renewal that occurs in the olfactory system. 1) A coarse topographic map divides the main olfactory system into at least four compartments and the accessory olfactory system into two compartments. They will analyze the determinants of compartmentalization by isolating and characterizing the molecules that restrict the termination sites of axon subsets. The ability of these molecules to influence axon trajectories will be tested on primary cell cultures of olfactory neurons. The structural determinants of compartmentalization will be investigated using light and electron microscopy in conjunction with immunocytochemical studies of intact olfactory bulbs. 2) There is a spatial and temporal pattern of expression of axonal and extracellular matrix adhesion molecules that provides a basis for subsets of axons to grow along designated pathways. One of these adhesion mechanisms in the olfactory system utilizes an endogenous carbohydrate binding protein, L-14, that is capable of inducing axon-axon and axon-matrix interactions. The investigators will analyze the role of this adhesion mechanism during development of olfactory connections, using mutant mice deficient in the extracellular matrix glycoprotein merosin, a key component of this adhesion mechanism. 3) Neuronal activity plays a role in stabilizing specific connections, leading to refinement of a coarse olfactory map. They will analyze the effects of changing neuronal activity through sensory deprivation on the precision of connections made by a small group of chemically defined neurons. The developmental relationship of the olfactory system and the forebrain is clinically significant. X-linked Kallmann syndrome is caused by a defect in the development of the olfactory system. These studies will provide insight into the molecular and cellular basis of olfactory structure and function and will illuminate specific mechanisms of axonal growth in normal and abnormal nervous systems.

描述： 哺乳动物的嗅觉系统被认为能够 区分数千种气味。细微差别 有些气味的分子结构会导致气味发生巨大的变化 洞察力。现在我们知道，嗅觉的第一步 辨别涉及气味与气味受体的相互作用 作用于鼻腔内的感觉神经元。大脑如何决定哪个 受体是否被激活仍然是个谜。然而，正如大多数 感觉系统，嗅觉系统可能使用定义的空间 受体激活模式以在大脑中建立连接。这 该提案的总体目标是确定身份， 参与空间的分子的结构和功能 嗅觉感觉神经元之间的连接组织 鼻腔及其轴突终止部位位于嗅球。这 研究人员提出了三种不同的机制 对于特定嗅觉连接的形成很重要，并且在 嗅觉系统中发生的持续神经更新。 1）A 粗略地形图将主要嗅觉系统至少划分为 四个隔室和附件嗅觉系统分为两个 隔间。他们将分析划分的决定因素 通过分离和表征限制的分子 轴突子集的终止位点。这些分子的能力 影响轴突轨迹将在原代细胞培养物上进行测试 嗅觉神经元。区隔化的结构决定因素 将使用光学和电子显微镜结合进行研究 对完整嗅球进行免疫细胞化学研究。 2）有 轴突和细胞外表达的空间和时间模式 基质粘附分子为轴突子集提供基础 沿着指定的路径成长。这些粘附机制之一 嗅觉系统利用内源性碳水化合物结合蛋白， L-14，能够诱导轴突-轴突和轴突-基质相互作用。 研究人员将分析这种粘附机制在 使用缺乏嗅觉连接的突变小鼠来发展嗅觉连接 细胞外基质糖蛋白 merosin，其关键成分 粘附机制。 3）神经元活动发挥稳定作用 特定的连接，从而细化粗略的嗅觉图。 他们将通过以下方式分析改变神经元活动的影响 对一小群人建立的联系的精确性的感觉剥夺 化学定义的神经元。的发展关系 嗅觉系统和前脑具有临床意义。 X连锁 卡尔曼综合症是由于大脑发育缺陷引起的 嗅觉系统。这些研究将深入了解分子 嗅觉结构、功能和意志的细胞基础 阐明正常和异常轴突生长的具体机制 神经系统。