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: 7448764
• 负责人: JAY Z PARRISH
• 金额: $ 8.54万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-02 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7448764
• 关键词: Affect; Afferent Neurons; Alleles; Axon; Biological; Cells; Class; Confocal Microscopy; Defect; Dendrites; Development; Disease; Down Syndrome; Drosophila genus; Foundations; Future; Gene Expression; Genes; Genetic; Genetic Screening; Genetic Techniques; Lasers; Lead; Life; Link; Maintenance; Mediating; Mental Retardation; Microsurgery; Molecular; Monitor; Mutation; Neurodegenerative Disorders; Neurons; Numbers; Pathway interactions; Patients; Pattern; Phase; Phosphotransferases; Polycomb; Post-Translational Protein Processing; Property; Regulation; Sensory; Synapses; Time; cell type; design; gene function; genetic analysis; insight; laser capture microdissection; mutant; novel; receptive field; research study

DESCRIPTION (provided by applicant): 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, almost nothing is known about how dendrites are maintained after establishment of receptive fields. The long-term objectives of this study are to define mechanisms that regulate dendrite maintenance in different neuronal types. The general approach is to use genetic techniques to identify mutant alleles that cell-autonomously affect dendrite maintenance. Detailed genetic and cell-biological analyses of these alleles and subsequent characterization of the neuronal function of the genes they disrupt should provide a basic understanding of mechanisms regulating dendrite maintenance. The specific aims of this study are to characterize the properties of dendrite maintenance in a specific class of Drosophila sensory neurons in which a genetic pathway for dendrite. maintenance has been identified, investigate the underlying mechanisms that regulate maintenance in this neuronal class, and identify additional modes of dendrite maintenance in this and other types of sensory neurons. Defects in dendrite maintenance should lead to loss of synaptic or sensory inputs, defects in neuronal circuits and likely contribute to a number of disease states. In fact, dendrite defects are the strongest correlate with mental retardation and layer III cortical neurons display a progressive loss of dendrites in Down syndrome. Therefore, understanding the phenomenon of dendrite maintenance and its underlying mechanisms has important implications for disease, particularly neurodegenerative disorders. Relevance Dendrite defects are among the strongest pathalogical correlates of mental retardation, but how dendrite formation is regulated during development and deregulated in disease is poorly understood. After dendrites cover their receptive field, they maintain their coverage with very litlle structural change, and this is likely important for proper function of neuronal circuits. Progressive dendrite defects have been observed in Down Syndrome patients, so a better understanding of dendrite maintenance will likely provide important information for our understaing of Down Syndrome and other neurodegenerative disorders.

描述(由申请人提供)： 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。虽然在理解树突如何占据它们的领地方面取得了进展，但几乎不知道树突在接受野建立后是如何维持的。这项研究的长期目标是确定在不同类型神经元中调节树突维持的机制。通常的方法是使用基因技术来识别细胞自主影响树突维持的突变等位基因。对这些等位基因的详细遗传和细胞生物学分析，以及随后对它们破坏的基因的神经功能的表征，应该会提供对调节树突维持的机制的基本理解。这项研究的具体目的是描述一类特定的果蝇感觉神经元的树突维持特性，在这类感觉神经元中，树突的遗传途径。维持已被识别，研究在这类神经元中调节维持的潜在机制，并在这类和其他类型的感觉神经元中识别树突维持的其他模式。树突维持的缺陷会导致突触或感觉输入的丧失，神经元回路的缺陷，并可能导致许多疾病状态。事实上，树突缺陷与智力低下的相关性最强，在唐氏综合症中，第三层皮质神经元显示出树突的进行性丢失。因此，了解树突维持现象及其潜在机制对疾病，特别是神经退行性疾病具有重要意义。树突缺陷是导致智力低下的最重要的病理因素之一，但是树突的形成在发育过程中是如何被调节的，在疾病中是如何被解除调节的，人们对此知之甚少。在树突覆盖它们的感受野之后，它们以很小的结构变化维持它们的覆盖，这对于神经元回路的正常功能可能是重要的。在唐氏综合症患者中观察到了进行性树突缺陷，因此更好地了解树突的维持可能会为我们了解唐氏综合征和其他神经退行性疾病提供重要信息。