Pattern Formation in the Sympathetic Nervous System

交感神经系统的模式形成

• 批准号: 6547792
• 负责人: CYNTHIA J FOREHAND
• 金额: $ 34.77万
• 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/6547792
• 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既表现为节段内模式，即注定要向交感神经链的细胞位于节段的尾部，而那些向交感神经链的细胞位于节段的尾部；也表现为节段间模式，即在脊髓节段内，沿背尾轴的节段位置决定了向侧或向尾端突出的细胞的数量。证据表明，基于它们投射到交感神经链的模式，神经节前细胞包括两个不同的群体。首先，单个细胞向交感神经链上或向尾侧投射，但很少同时向两个方向投射。其次，对近轴中胚层的操作，如将外源性维甲酸或成纤维细胞生长因子应用于发育中的体体，或将体体沿背尾轴转位，会不同地改变节前细胞池。这些研究表明，胸脊髓神经节前细胞柱的投射模式在发育早期受到外周信号的影响。我们假设，神经节前神经元具有一种固有的身份，即作为喙侧或尾侧突出的细胞，这种身份在早期发育中由调节模式形成的基因指定。该应用程序的具体目的是为了阐明在交感神经节前细胞柱中指定神经元身份的机制。前三个目标将确定调节该系统模式的信号提示何时何地可能起作用。最后两个目的将测试一个特定的假设，即交感神经节前细胞柱投射模式中指定节间梯度的位置信息是由Hox基因和控制Hox表达的基因调节的。具体目标是：确定某些操作对神经节前细胞柱模式影响的时间限制。具体目标2。为了验证背侧突起的神经节前神经元先于尾侧突起的神经节前神经元出生的假说。具体目标3。为了验证相对于躯体运动神经元，节前神经元轴突离开脊髓的时间延迟的假设。具体目标为了验证特定神经节前细胞类型沿胸脊髓纵轴的分布是由Hox编码决定的假设。5.具体目标为了验证节前细胞柱模式的Hox编码规范是由Polycomb/Trithorax调节蛋白组成员调节的假设。