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

基本信息

批准号：
7998972
负责人：
JAY Z PARRISH
金额：
$ 24.89万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-21 至 2013-04-30
项目状态：
已结题

项目摘要

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.

树突树皮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其领土方面取得了进展，但很少知道神经元如何保持其接受场的树突状覆盖范围。由于树突缺陷是与智力低下的最强相关，了解树突维持的现象及潜在的机制对疾病，尤其是神经退行性疾病具有重要意义。然而，技术局限性使树突维持在很大程度上是棘手的现象。这这项研究的长期目的是定义调节不同的树突维持的机制神经元类型。一般方法是使用基因筛查和基于微阵列的基因表达分析以识别细胞自主调节树突维持的基因。详细的遗传和细胞生物学这些基因神经元功能的分析应提供对机制的基本理解调节树突维护。这项研究的具体目的是（1）识别用于用于的基因树突维持和突变定义果蝇感觉中的树突维持的不同模式神经元，（2]以从建立维护接受田间覆盖范围，以及（3）以深入了解建立和如何建立和在给定的神经元中维护接受场覆盖范围。