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。尽管在阐明轴突引导的机制方面取得了巨大进展，但对轴突如何在神经束的特定区域内呈现的知之甚少。我们建议在秀丽隐杆线虫中研究这个问题，重点是HSN轴突。建立整个神经系统后，HSN轴突沿着腹神经绳延伸。 HSN生长锥沿PVQ和PVP轴突筋膜，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提示。虽然对哺乳动物神经内的轴突如何吸引人，但最近的发现表明，在神经内的嗅觉轴突对嗅球的靶向很重要。 HSN可以为这种神经如何在哺乳动物中组织起来提供模型。该提案具有三个具体目标。在第一个目标中，使用抓握将标记不同轴突之间的界面。在第二个目标中，将开发出RNAi鉴定涉及HSN轴突诱惑基因的方法。这些方法应绕过由基本基因的RNAi引起的致命作用，并绕过其他轴突偶然缺陷引起的间接作用。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筋膜中的作用。 公共卫生相关性：了解这些轴突如何找到其目标是神经发育中的一个基本问题。尽管在阐明轴突引导的机制方面取得了巨大进展，但对轴突如何沿神经束的特定区域生长的知之甚少。我们建议在秀丽隐杆线虫中研究这个问题，秀丽隐杆线虫是一种模型生物体，在轴突指导的定义保守分子中发挥了作用。