GLYCOCONJUGATES IN CELL-CELL INTERACTIONS

描述：哺乳动物的嗅觉系统被认为能够 在成千上万种气味中辨别。两者之间的细微差别 某些气味的分子结构会导致气味的剧烈变化 感知力。现在已经知道，嗅觉的第一步 辨别涉及气味与气味感受器的相互作用 鼻腔中的感觉神经元。大脑是如何决定 受体是否被激活仍是一个谜。然而，在大多数情况下， 感觉系统，嗅觉系统可能使用定义的空间 在大脑中建立连接的受体激活模式。这个 这项提案的总体目标是确定身份， 参与空间结构的分子的结构和功能 嗅觉感觉神经元之间联系的组织 鼻腔及其在嗅球内的轴突终末部位。这个 调查人员提出了三种不同的机制，可能是 在形成特定的嗅觉连接方面很重要，而且在 嗅觉系统中持续不断的神经更新。1)A 粗略的地形图将主要嗅觉系统至少分为 四个隔室和辅助嗅觉系统分成两个 车厢。他们将分析划分的决定因素 通过分离和表征限制分子的 轴突亚群的终末部位。这些分子的能力 影响轴突轨迹将在原代细胞培养上进行测试 嗅觉神经元。划分的结构性决定因素 将结合使用光学和电子显微镜进行研究 对完整的嗅球进行免疫细胞化学研究。2)有 轴突和细胞外表达的时空模式 基质黏附分子，为轴突亚群提供基础 沿着指定的道路成长。这些黏附机制中的一种 嗅觉系统利用一种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连机制在 利用嗅觉连接基因缺失的突变小鼠发展嗅觉连接 细胞外基质糖蛋白Merosin是这一过程的关键成分 粘着机制。3)神经元活动起稳定作用。 特定的连接，导致粗略嗅觉地图的精细化。 他们将通过以下方式分析改变神经元活动的影响 对一小群人建立的连接的精确性的感觉剥夺 化学定义的神经元。三个民族的发展关系 嗅觉系统和前脑具有重要的临床意义。X-链接 Kallmann综合征是由发育中的缺陷引起的 嗅觉系统。这些研究将提供对分子的洞察。 以及嗅觉结构、功能和意志的细胞基础 阐明正常和异常情况下轴突生长的具体机制 神经系统。

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.