Glycoconjugates in Cell Cell Interactions

描述：本项目的主要目标是阐明 嗅觉系统中潜在的轴突引导，使用啮齿动物模型。多数 哺乳动物物种，包括人类，有能力区分数千种 不同的气味。这种能力编码在建立的有组织的连接中 鼻腔嗅觉感觉神经元与中枢神经元间的关系 嗅球。感觉神经元轴突在鼻腔内广泛分布 空洞会聚到一小部分称为肾小球的靶子上，这些靶子已经固定 嗅球的位置。相反，来自邻近感官的轴突 在嗅球中，神经元分化成宽泛的区域。这项建议 重点关注占据轴突的细胞和细胞外基质蛋白 通路和围绕嗅球的嗅神经层。这个 存在于这些区域的主要细胞类型是一种特殊类型的胶质细胞 (成鞘细胞)是嗅觉系统所特有的。这是假设的 包膜细胞在分子上是异质性的，因此呈现出一种 嗅觉轴突延伸到神经层时所处的不同环境 嗅球的颜色。特定的成鞘细胞亚群已经被 显示为同时呈现允许和不允许的环境 嗅轴突的独特子集。我们建议制作一张地图， 神经层的允许和非允许区域，定义 引导线索及其调节的轴突的表达。我们会扰乱 神经层轴突与引导线索的相互作用 胚胎嗅觉组织切片培养及功能研究 在一个完整系统中的活动。我们还将分析包裹体的发展 细胞，特别是调节前体细胞从 嗅觉上皮至嗅球的神经层。这些研究 旨在拓宽我们对用于组织的机制的了解 哺乳动物神经系统中的连接。

DESCRIPTION: The main objective of this project is to elucidate the mechanisms underlying axon guidance in the olfactory system, using rodent models. Most mammalian species, including humans, have the ability to distinguish thousands of different odors. This ability is encoded in the organized connections made between olfactory sensory neurons in the nasal cavity and CNS neurons in the olfactory bulb. Axons from sensory neurons distributed widely in the nasal cavity converge onto a small number of targets called glomeruli that have fixed positions in the olfactory bulb. Conversely, axons from neighboring sensory neurons diverge to broadly defined zones in the olfactory bulb. This proposal focuses on the cells and extracellular matrix proteins that occupy axon pathways and the olfactory nerve layer that surrounds the olfactory bulb. The main cell type present in these regions is a special type of glial cell (ensheathing cell) that is unique to the olfactory system. It is hypothesized that ensheathing cells are molecularly heterogeneous and therefore present a differential environment to olfactory axons as they extend into the nerve layer of the olfactory bulb. Specific subpopulations of ensheathing cells have been shown to simultaneously present a permissive and non-permissive environment to unique subsets of olfactory axons. We propose to construct a map of the permissive and non-permissive regions of the nerve layer, defining the expression of guidance cues and the axons that they regulate. We will perturb interactions between axons and guidance cues in the nerve layer in vivo and in slice cultures of embryonic olfactory tissue in order to demonstrate functional activity in an intact system. We will also analyze development of ensheathing cells, in particular, the regulation of migration of precursor cells from the olfactory epithelium to the nerve layer of the olfactory bulb. These studies are intended to broaden our knowledge of mechanisms used to organize connections in the mammalian nervous system.