Genetic Screen for Zebrafish Neural Defect Mutants

斑马鱼神经缺陷突变体的遗传筛查

• 批准号: 7691584
• 负责人: Bruce H Appel
• 金额: $ 31.65万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7691584
• 关键词: Affect; Axon; Biological Assay; Biological Models; Cell Communication; Cells; Cellular Morphology; Chemicals; Coupled; Defect; Development; Disease; Embryo; Family; Foundations; Genes; Genetic; Genetic Screening; Goals; Image; Induced Mutation; Injury; Investigation; Knowledge; Larva; Lead; Life; Location; Maps; Mediating; Membrane; Modeling; Molecular; Morphology; Motor; Mutagenesis; Mutate; Mutation; Nerve; Nervous System Physiology; Nervous system structure; Neuraxis; Neuroglia; Neurons; Oligodendroglia; Peripheral; Peripheral Nerves; Peripheral Nervous System; Phenotype; Population; Proteins; Reporter; Research Personnel; Resolution; Schwann Cells; Series; Stem cells; Techniques; Time; Transgenic Organisms; Work; Zebrafish; base; cell behavior; design; effective therapy; experience; gene discovery; in vivo; injured; migration; mutant; nervous system disorder; neural circuit; neurodevelopment; neuron development; public health relevance; red fluorescent protein; relating to nervous system; repaired; sensory system; transmission process

DESCRIPTION (provided by applicant): The long-term goal of this project is to identify the genes that are required to build a nervous system. The nervous system is composed of two general classes of cells: neurons, which transmit information in the form of electrical impulses, and glial cells, which facilitate impulse transmission and survival of neurons. How neurons and glial cells are formed and organized into functional neural circuits during development is still poorly understood. The project design draws from the well-validated idea that mutations that disrupt neural development reveal critical genes. Building on the expertise of the collaborating team of investigators, this work will discover genes that are necessary for development of motor axons and glial cells that wrap central and peripheral nerves. The project will use zebrafish as a model system, which permits the careful observations necessary to find rare mutations that cause specific neural defects. The first aim of the project is to screen families of mutagenized zebrafish embryos for defects of motor axons and two distinct populations of central and peripheral myelinating glial cells by examining expression of transgenically encoded fluorescent reporter proteins that reveal cell morphologies. The second aim is to determine how each mutation causes its corresponding defect through careful characterization of cellular defects, using immunohistochemical and transgenic cell marking techniques and in vivo time-lapse imaging. The third aim is to determine the chromosomal location of each mutation and identify the affected genes. Completion of this project will enhance understanding of the genetic bases of neurological disorders involving the sensory system or glia and provide genes that might be used to promote neural repair following injury or disease. PUBLIC HEALTH RELEVANCE: This project will identify genes that are necessary to build a nervous system. It will provide a better understanding of how the nervous system develops and potentially lead to new strategies to promote neural repair following disease or injury.

描述（由申请人提供）：该项目的长期目标是确定建立神经系统所需的基因。神经系统由两种一般细胞组成：神经元以电脉冲的形式传输信息和神经胶质细胞，这些信息促进了脉冲传播和神经元的存活。在发育过程中，神经元和神经元细胞如何形成并组织成功能性神经回路。该项目设计借鉴了验证良好的观念，即破坏神经发育的突变揭示了关键基因。这项工作以调查人员的合作团队的专业知识为基础，将发现开发轴突和神经胶质细胞所必需的基因，这些基因包裹中央和周围神经。该项目将使用斑马鱼作为模型系统，该系统允许仔细的观察结果找到引起特定神经缺陷的稀有突变。该项目的第一个目的是通过检查揭示细胞形态的转基因编码的荧光记者蛋白的表达来筛选诱变的斑马鱼胚胎的家庭，以使运动轴突的缺陷以及两个不同的中央和周围髓髓胶质细胞种群来筛选胶质神经胶质细胞的两个不同种群。第二个目的是通过使用免疫组织化学和转基因细胞标记技术以及体内延时成像来确定每个突变如何通过仔细表征细胞缺陷来导致其相应的缺陷。第三个目的是确定每个突变的染色体位置并确定受影响的基因。该项目的完成将增强对涉及感觉系统或神经胶质的神经系统疾病的遗传基础的理解，并提供可用于促进损伤或疾病后神经修复的基因。公共卫生相关性：该项目将确定建立神经系统所需的基因。它将更好地了解神经系统如何发展并有可能导致疾病或损伤后促进神经修复的新策略。