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。尽管在了解树突如何占据其领土方面已经取得了进展，但知之甚少。了解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的相关性最强，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影响。然而，技术限制使得枝晶维持成为一种非常棘手的现象。这这项研究的长期目标是定义调节不同树突维持的机制神经元类型。一般方法是使用遗传筛查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。详细的遗传和细胞生物学对这些基因的神经元功能的分析应该提供对机制的基本理解调节树突的维护。本研究的具体目的是（1）鉴定所需的基因树突维持和突变定义果蝇感觉中树突维持的不同模式神经元，（2）表征神经元从神经元转变时发生的分子和细胞生物学变化建立以维持感受野覆盖范围，以及（3）深入了解如何建立和感受野覆盖的维持在给定的神经元中协调。