Approaches to studying axon fasciculation

研究轴突束颤的方法

• 批准号: 8146134
• 负责人: GIAN GARRIGA
• 金额: $ 18.8万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8146134
• 关键词: Acetylcholine; Address; Affect; Animal Model; Animals; Axon; Biological; Bypass; Caenorhabditis elegans; Cells; Cues; Defect; Development; Essential Genes; Fluorescence; Genes; Genetic Models; Goals; Growth Cones; Label; Mammals; Modeling; Muscle fasciculation; Nerve; Nervous system structure; Neurons; Neurotransmitters; Play; RNA Interference; Role; Side; Signal Transduction; Sorting - Cell Movement; Synapses; Techniques; Testing; Time; axon guidance; design; mutant; neurodevelopment; olfactory bulb; public health relevance; research study; tool

DESCRIPTION (provided by applicant): Understanding how axons find their synaptic targets is a fundamental problem in neurodevelopment. While great progress has been made in elucidating the mechanisms of axon guidance, less is known about how axons fasciculate within specific regions of a nerve bundle. We propose to study this problem in C. elegans with a focus on the HSN axon. The HSN axon extends along the ventral nerve cord after the entire nervous system has been established. The HSN growth cone fasciculates along the PVQ and PVP axons, and the short-term goal of this project is to identify the cues that define the HSN's ability to grow along its specific path in the nerve bundle. While little is known about how axons fasciculate within mammalian nerves, recent findings suggest that sorting of olfactory axons within the nerve are important in their targeting at the olfactory bulb. The HSN may provide a model for how such nerves are organized in mammals. The proposal has three specific aims. In the first aim, the interface between the different axons will be labeled using GRASP. In the second aim, RNAi approaches to identify genes involved in HSN axon fasciculation will be developed. These approaches should bypass the lethal effects caused by RNAi of essential genes and indirect effects caused by earlier defects in the fasciculation of other axons. In the third aim, the approaches will be tested to elucidate the role of the neurotransmitter acetylcholine in axon fasciculation.. PUBLIC HEALTH RELEVANCE: Understanding how these axons find their targets is a fundamental problem in neurodevelopment. While great progress has been made in elucidating the mechanisms of axon guidance, less is known about how axons grow along specific regions of a nerve bundle. We propose to study this problem in C. elegans, a model organism that has been instrumental in defined conserved molecules that function axon guidance.

描述（由申请人提供）：了解轴突如何找到其突触目标是神经发育中的一个基本问题。虽然在阐明轴突引导机制方面已经取得了巨大进展，但对于轴突如何在神经束的特定区域内束动却知之甚少。我们建议研究线虫中的这个问题，重点关注 HSN 轴突。整个神经系统建立后，HSN 轴突沿着腹神经索延伸。 HSN 生长锥沿着 PVQ 和 PVP 轴突成束，该项目的短期目标是确定定义 HSN 沿着神经束中特定路径生长的能力的线索。虽然人们对哺乳动物神经中的轴突如何成束知之甚少，但最近的研究结果表明，神经内嗅觉轴突的分类对于它们瞄准嗅球非常重要。 HSN 可以为哺乳动物中此类神经的组织方式提供一个模型。该提案有三个具体目标。在第一个目标中，不同轴突之间的界面将使用 GRASP 进行标记。第二个目标是开发 RNAi 方法来鉴定参与 HSN 轴突束颤的基因。这些方法应该绕过必需基因 RNAi 引起的致命效应以及其他轴突束状运动早期缺陷引起的间接效应。在第三个目标中，将测试这些方法以阐明神经递质乙酰胆碱在轴突束颤中的作用。 公共健康相关性：了解这些轴突如何找到它们的目标是神经发育的一个基本问题。虽然在阐明轴突引导机制方面已经取得了巨大进展，但对于轴突如何沿着神经束的特定区域生长却知之甚少。我们建议在线虫中研究这个问题，线虫是一种模式生物，在定义具有轴突引导功能的保守分子方面发挥了重要作用。