CONTROL OF SEGMENT-SPECIFIC PREGANGLIONIC AXON OUTGROWTH

描述（申请人的摘要）：交感节前神经元 表现出一种节段内模式，其中细胞注定要投射 尾侧进入交感神经链的神经节位于节段的吻侧， 而那些投射到交感神经链尾部的神经元位于 尾在段，和一个节间的模式，其中的数量 在脊髓节段内， 由沿吻尾轴的节段位置沿着确定。 有 有证据表明节前细胞有两个区域组， 根据它们投射到交感神经链的模式。 第一、 单个细胞向吻侧或尾侧投射到交感神经 链，但很少在两个方向。 第二，操纵 外周，如应用外源性视黄酸（RA）或 易位或体节沿着喙尾轴，差异改变 节前细胞池 这些研究首次提供了 证明了在节前神经节中细胞增殖和/或存活 胸脊髓中的细胞柱受外周线索的影响 早期发展。 我们假设节前神经元有一个 固有的身份，无论是吻或尾突出的细胞。 的 本申请的特定目的是为了解决 神经节前池变得不同，分子信号是什么，在哪里， 是调节节前细胞数量的， 节前神经元对周围线索作出反应， 途径的选择，以及破坏正常的 本系统中的模式规则是为了功能组织， 自主神经系统 具体目标是：1. 以确定 节前神经元是否注定要向吻侧投射， 在早期发育中受到谱系限制。 2. 确定 外源性FGF治疗调节节前细胞大小的方式 人口。 3. 为了确定受体的差异表达 对于细胞外基质分子区分类别的节前 神经元和4. 为了确定是否改变了 一类交感节前神经元与伴随的 在细胞数量或神经支配密度的改变， 椎旁交感链神经节 了解监管 该系统的组织有可能提供一个独特的 研究人体地形图的一般方法的情况 与不同层次的神经轴相匹配

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.