Genetic Analysis of Dendrite Maintenance in Drosophila Sensory Neurons

果蝇感觉神经元树突维持的遗传分析

• 批准号: 8257545
• 负责人: JAY Z PARRISH
• 金额: $ 24.08万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-21 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8257545
• 关键词: Affect; Afferent Neurons; Alleles; Axon; Biological; Cells; Confocal Microscopy; Defect; Dendrites; Development; Disease; Down Syndrome; Drosophila genus; Foundations; Future; Gene Expression Profile; Gene Expression Profiling; Genes; Genetic; Genetic Screening; Lasers; Life; Link; Maintenance; Mediating; Mental Retardation; Microsurgery; Molecular; Monitor; Mutation; Neurodegenerative Disorders; Neurons; Pathway interactions; Patients; Pattern; Phase; Phosphotransferases; Polycomb; Post-Translational Protein Processing; Property; Proteins; Regulation; Reverse Transcriptase Polymerase Chain Reaction; Time; base; cell type; design; gene function; genetic analysis; insight; laser capture microdissection; mutant; novel; receptive field; research study

Dendrite arborization patterns are a hallmark of neuronal type and a critical determinant of neuronal function. Although progress has been made in understanding how dendrites come to occupy their territory, very little is known about how neurons maintain dendritic coverage of their receptive field. Since dendrite defects are the strongest correlate with mental retardation, understanding the phenomenon of dendrite maintenance and its underlying mechanisms has important implications for disease, particularly neurodegenerative disorders. Nevertheless, technical limitations have made dendrite maintenance a largely intractable phenomenon. The long-term objectives ofthis study are to define mechanisms that regulate dendrite maintenance in different neuronal types. The general approach is to use genetic screening and microarray-based gene expression profiling to identify genes that cell-autonomously regulate dendrite maintenance. Detailed genetic and cellbiological analyses ofthe neuronal function of these genes should provide a basic understanding of mechanisms regulating dendrite maintenance. The specific aims ofthis study are (1) to identify genes that are rquired for dendrite maintenance and mutationally define different modes of dendrite maintenance in Drosophila sensory neurons, (2] to characterize the molecular and cell-biological changes that occur as a neuron transitions from establishing to maintaining receptive field coverage, and (3) to gain insight into how establishment and maintenance of receptive field coverage are coordinated in a given neuron.

树突分枝模式是神经元类型的标志，也是神经元功能的关键决定因素。 尽管在理解树突如何占据它们的领地方面取得了进展，但很少有进展。 已知神经元如何维持其感受野的树突覆盖。由于枝晶缺陷是 与智力低下有最强的相关性，了解树突维持现象及其 潜在的机制对疾病，特别是神经退行性疾病有着重要的影响。 尽管如此，技术上的限制使得树枝晶的维持在很大程度上是一个棘手的现象。这个 这项研究的长期目标是确定在不同的环境中调节树突维持的机制 神经元类型。通常的方法是使用遗传筛选和基于微阵列的基因表达 分析以确定细胞自主调节树突维持的基因。详细的遗传学和细胞生物学 对这些基因的神经功能的分析应该提供对机制的基本理解 规范树枝晶的维护。这项研究的具体目的是(1)确定需要的基因 果蝇感觉中的树突维持和突变定义不同的树突维持模式 神经元，(2)描述当神经元从 建立到保持可接受的现场覆盖，以及(3)深入了解建立和 感受野覆盖的维持是在一个给定的神经元中协调的。