Neural Circuitry in the Developing Zebrafish Spinal Cord

斑马鱼脊髓发育中的神经回路

• 批准号: 6854786
• 负责人: MARK M VOIGT
• 金额: $ 7.35万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6854786
• 关键词: developmental genetics; developmental neurobiology; genetic markers; genetic screening; genetically modified animals; intercellular connection; neural information processing; neuroanatomy; neurochemistry; reporter genes; spinal cord; vertebrate embryology; zebrafish

DESCRIPTION (provided by applicant): A zebrafish embryo goes from a single-cell to an organism with a functioning nervous system within its first 24 hours of existence. By 24 hours post-fertilization, the embryo has mechanosensory-mediated reflex motor behaviors and by 96 hr the fish is a free-swimming larva. The manifestation of these behaviors is due to the establishment of a simple but effective neural network in the spinal cord and hindbrain of the developing fish. This simple nervous system provides the scaffolding for further expansion during maturation of the organism. Elucidating the mechanisms underlying early nervous system formation in the zebrafish could have a huge impact on our understanding of how many neurological disorders arise in man. The properties of the embryonic/larval zebrafish has made it uniquely suited to study the formation of a neural network- it's fertilized externally, transparent during its development and lends itself easily to molecular techniques such as anti-sense treatment and transgenesis. Anatomical studies using dye labeling have yielded information regarding the morphologies of spinal neurons during these early time points, suggesting the presence of some 11-15 neurons per hemi-segment of the cord between 24-96 HPF. In addition, these studies have provided some insight into how the neurons connect to one another to form a network. However, almost nothing is known about how these neurons communicate amongst each other. It is the purpose of this proposal to generate transgenic fish lines that will enable the elucidation of the neurochemical anatomy of the developing spinal cord. Not only will these fish provide information as to the connectivity of the various spinal and supraspinal pathways, but they will also provide markers for use in functional studies utilizing either co-expression (e.g., with calcium indicators) or electrophysiological approaches. In addition, they can provide markers for specific neuronal types that can be used in forward genetic screens aimed at identifying genes required for either phenotype or connectivity decisions in these cells

描述（申请人提供）：斑马鱼胚胎在其存在的前24小时内从单细胞变成具有功能神经系统的生物体。受精后24小时，胚胎具有机械感觉介导的反射运动行为，96小时，鱼是一个自由游泳的幼虫。这些行为的表现是由于发育中的鱼在脊髓和后脑中建立了一个简单但有效的神经网络。这个简单的神经系统为生物体成熟过程中的进一步扩张提供了支架。阐明斑马鱼早期神经系统形成的机制可能会对我们理解人类有多少神经系统疾病产生巨大影响。胚胎/幼体斑马鱼的特性使其特别适合研究神经网络的形成-它在外部受精，在发育过程中是透明的，并且很容易适用于反义治疗和转基因等分子技术。使用染料标记的解剖学研究已经产生了关于在这些早期时间点期间脊髓神经元的形态学的信息，表明在24-96 HPF之间，脊髓的每半段存在约11-15个神经元。此外，这些研究还为神经元如何相互连接形成网络提供了一些见解。然而，几乎没有人知道这些神经元是如何相互交流的。这是本提案的目的，以产生转基因鱼线，这将使发展中的脊髓的神经化学解剖的说明。这些鱼不仅将提供关于各种脊髓和脊髓上通路的连接性的信息，而且它们还将提供用于利用共表达（例如，用钙指示剂）或电生理学方法。此外，它们可以提供特定神经元类型的标记物，这些标记物可用于正向遗传筛选，目的是鉴定这些细胞中表型或连接决定所需的基因