Pattern Formation in the Sympathetic Nervous System

交感神经系统的模式形成

• 批准号: 6934557
• 负责人: CYNTHIA J FOREHAND
• 金额: $ 35.98万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934557
• 关键词: axon; biological signal transduction; cell cell interaction; cell differentiation; cell migration; chick embryo; cues; developmental neurobiology; electroporation; gene expression; genetic regulation; homeobox genes; in situ hybridization; mesoderm; motor neurons; neural plate /tube; neuronal guidance; protein structure function; spinal cord; sympathetic nervous system

DESCRIPTION (provided by applicant): Sympathetic preganglionic neurons exhibit both an intrasegmental pattern, in which cells destined to project rostrally 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. Evidence suggests that preganglionic cells comprise two distinct 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 paraxial mesoderm, such as application of exogenous retinoic acid or fibroblast growth factor to the developing somites, or transposition of somites along the rostrocaudal axis, differentially alter the preganglionic cell pools. These studies demonstrate that the pattern of projections from 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 and that this identity is specified in early development by genes that regulate pattern formation. The specific aims of this application are designed to elucidate the mechanisms that specify neuronal identity in the sympathetic preganglionic cell column. The first three aims will determine when and where signaling cues that regulate pattern in this system might act. The last two aims will test the specific hypothesis that the positional information that specifies the intersegmental gradient in the pattern of projections from the sympathetic preganglionic cell column is regulated by Hox genes and the genes that control Hox expression. The specific aims are: Specific Aim 1.To determine the temporal limits of the effect of somite manipulations on pattern in the preganglionic cell column. Specific Aim 2. To test the hypothesis that rostrally projecting preganglionic neurons are born before caudally projecting preganglionic neurons. Specific Aim 3. To test the hypothesis that preganglionic neuronal axons exit the spinal cord with a temporal delay relative to somatic motor neurons. Specific Aim 4. To test the hypothesis that the distribution of specific preganglionic cell types along the longitudinal axis of the thoracic spinal cord is determined by the Hox code. Specific Aim 5. To test the hypothesis that Hox code specification of pattern in the preganglionic cell column is regulated by members of the Polycomb/Trithorax group of regulatory proteins.

描述（由申请人提供）：交感神经节前神经元表现出节内模式，其中注定要向交感链突出的细胞位于节段的喙部，而那些向尾部突出进入交感链的细胞则位于节段的尾部，以及节间模式，其中脊柱节段内向嘴部或尾部突出的细胞的数量由沿节段的节段位置决定。的 颈尾轴。有证据表明，根据其投射到交感神经链的模式，节前细胞包含两个不同的群体。首先，单个细胞从头侧或尾侧投射到交感神经链中，但很少在两个方向上投射。其次，对近轴中胚层的操作，例如对发育中的体节应用外源性视黄酸或成纤维细胞生长因子，或沿头尾轴转位体节，会差异性地改变节前细胞池。这些研究表明，胸脊髓节前细胞柱的投射模式受到发育早期外周信号的影响。我们假设节前神经元具有作为头侧或尾侧突出细胞的固有特性，并且这种特性在早期发育中由调节模式形成的基因指定。该应用的具体目标是阐明交感神经节前细胞柱中指定神经元身份的机制。前三个目标将决定调节该系统模式的信号线索何时何地发挥作用。最后两个目标将检验特定假设，即指定交感神经节前细胞柱投影模式中节段间梯度的位置信息受 Hox 基因和控制 Hox 表达的基因调节。具体目标是： 具体目标 1.确定体节操作对节前细胞柱模式的影响的时间限制。具体目标 2. 检验以下假设：向尾部投射的节前神经元先于向尾部投射的节前神经元出生。具体目标 3. 检验节前神经元轴突相对于体细胞运动神经元以时间延迟退出脊髓的假设。具体目标 4. 检验特定节前细胞类型沿胸脊髓纵轴的分布由 Hox 代码确定的假设。具体目标 5. 检验以下假设：节前细胞柱中的 Hox 代码规范是由调节蛋白 Polycomb/Trithorax 组的成员调节的。