CONTROL OF SEGMENT-SPECIFIC PREGANGLIONIC AXON OUTGROWTH

描述(申请人摘要)：交感神经节前神经元 都表现出一种段内模式，在这种模式下，细胞注定要投射 进入交感神经链的尾部位于节段的吻部， 而向尾部投射到交感神经链的那些 在节段的尾部，以及节间模式，在该模式中， 在脊柱节段内的吻部或尾部投射细胞 由沿吻尾轴的节段位置确定。的确有 有证据表明节前细胞分为两个区群， 根据他们投射到交感神经链的模式。第一, 单个细胞在吻部或尾部投射到交感神经节 链状，但很少是双向的。第二，操纵 外周，如外源性维甲酸(RA)或 沿吻尾轴的移位或体节，差异改变 节前细胞池。这些研究提供了第一个 神经节前区细胞增殖和/或存活的证据 胸髓中的细胞柱受外周提示的影响 处于早期开发阶段。我们假设节前神经元有一个 作为嘴上或尾部突出的细胞的固有身份。这个 此应用程序的特定目标旨在解决当 节前池变得不同了，分子信号是什么和在哪里 是不是调节节前种群的大小， 节前神经元对外周提示做出反应，使适当的 路径选择，以及扰乱正常 本系统中对模式的调整是为了对 自主神经系统。具体目标是：1.确定 节前神经元是注定要投射到吻部还是 在尾部，在早期发育中受到血统限制。2.确定 外源性成纤维细胞生长因子对节前神经节大小的调节作用 人口。3.确定受体的差异表达是否 细胞外基质分子区分节前神经节的分类 神经元和4。以确定是否改变的数量或 交感神经节前神经元类与伴随性 神经细胞数量或神经分布密度的变化 椎旁交感神经节。理解规则中的 这一系统的组织有可能提供一个独特的 人体地形图的一般方法研究现状 与不同级别的神经轴相匹配。

DESCRIPTION (Applicant's Abstract): Sympathetic preganglionic neurons exhibit both an intrasegmental pattern, in which cells destined to project caudally into the sympathetic chain are located rostrally in the segment, while those that project caudally into the sympathetic chain are located caudally in the segment, and an intersegmental pattern, in which the number of rostrally or caudally projecting cells within a spinal segment is determined by the segmental position along the rostrocaudal axis. There is evidence to indicate that preganglionic cells are of two district groups, based on their pattern of projection into the sympathetic chain. First, individual cells project either rostrally or caudally into the sympathetic chain, but rarely in both directions. Second, manipulations of the periphery, such as application of exogenous retinoic acid (RA) or transposition or somites along the rostrocaudal axis, differentially alter the preganglionic cell pools. These studies have provided the first demonstration that cell proliferation and/or survival in the preganglionic cell column in the thoracic spinal cord is influenced by peripheral cues early in development. We hypothesize that preganglionic neurons have an inherent identity as either rostrally or caudally projecting cells. The specific aims of this application are designed to address when the preganglionic pools become different, what and where the molecular signals are that regulate the size of preganglionic populations, the way in which the preganglionic neurons respond to peripheral cues to make appropriate pathway choices, and what the implications of disrupting the normal regulation of pattern in this system are for the functional organization of the autonomic nervous system. The specific aims are: 1. To determine whether preganglionic neurons are fated to project either rostrally or caudally by lineage restrictions in early development. 2. To determine the way in which exogenous FGF treatment regulates the size of preganglionic populations. 3. To determine whether differential expression of receptors for extracellular matrix molecules distinguishes classes of preganglionic neuron and 4. To determine whether alterations in the number of either class of sympathetic preganglionic neurons is associated with concomitant alterations in either cell number or innervation density within the paravertebral sympathetic chain ganglia. Understanding the regulation of the organization of this system has the potential to provide a unique situation for studying the general way in which topographic maps of the body are matched to various levels of the neuraxis.