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; 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。微妙的差异 某些气味的分子结构会导致气味发生巨大变化 洞察力。现在众所周知，嗅觉的第一步 歧视涉及气味与气味受体的相互作用 在鼻腔中的感觉神经元上。大脑如何决定哪个 被激活的受体仍然是一个谜。但是，大多数 感觉系统，嗅觉系统可能使用定义的空间 受体激活的模式使大脑中的连接。这 该建议的总体目标是确定身份， 参与空间的分子的结构和功能 在嗅觉感觉神经元之间的连接组织 鼻腔及其在嗅球中的轴突终止位点。这 调查人员提出了三种不同的机制 对于特定嗅觉连接的形成和期间 嗅觉系统中发生的持续神经更新。 1）a 粗形地图将主要嗅觉系统划分为至少 四个隔间和配件嗅觉系统分为两个 车厢。他们将分析分隔的决定因素 通过隔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。分隔的结构决定因素 将使用光和电子显微镜进行研究 与完整嗅球的免疫细胞化学研究。 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亚集提供基础 沿指定的途径生长。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，能够诱导轴突轴和轴突 - 矩阵相互作用。 研究人员将分析这种粘附机制的作用 使用不足的突变小鼠的嗅觉连接的发展 细胞外基质糖蛋白梅罗蛋白，这是其中的关键组成部分 粘附机制。 3）神经元活动在稳定中起作用 特定连接，导致粗嗅图的细化。 他们将通过 一小组建立的连接精度的感觉剥夺 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 Kallmann综合征是由发展的缺陷引起的 嗅觉系统。这些研究将提供有关分子的洞察力 和嗅觉结构和功能的细胞基础，将 照明正常和异常的轴突生长的特定机制 神经系统。