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Genetic mechanisms controlling the visual pathway to the central complex of the Drosophila brain

控制果蝇大脑中央复合体视觉通路的遗传机制

基本信息

批准号：
9896874
负责人：
VOLKER HARTENSTEIN
金额：
$ 32.97万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2022-03-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9896874
关键词：
Address Adhesions Anatomy Anterior Ants Axon Bees Behavior Binding Biological Models Birth Birth Order Brain Candidate Disease Gene Cell Communication Cells Characteristics Complex Data Development Drosophila genus Elements Exhibits Eye Gene Expression Genes Genetic Genetic Markers Genetic study Human Image Individual Insecta Interneurons Knock-out Libraries Location Locomotion Maps Modeling Molecular Molecular Genetics Monitor Mus Nervous system structure Neurons Optic Lobe Optics Pathway interactions Pattern Perception Phenotype Play Process Property RNA Interference Recording of previous events Regulator Genes Reporter Research Role Semaphorins Shapes Sorting - Cell Movement Specific qualifier value Stereotyping Structure Synapses System Techniques Testing Therapeutic Time Vision Visual Visual Pathways Walking Work base brain circuitry cell type differential expression embryonic stem cell experimental study fly genetic analysis knock-down locomotor control locust mind control neuroblast neuronal circuitry orientation selectivity polarized light preservation progenitor public health relevance response sensory stimulus spatial relationship stem cells time interval tool transcriptome transcriptome sequencing two-photon virtual visual information visual stimulus

项目摘要

DESCRIPTION (provided by applicant): The studies of this application ask how gene expression controls neuronal connectivity and, thereby, brain function. This question is of general importance if one wants to understand, and (therapeutically) manipulate brain circuitry. We use the model system Drosophila, where virtually every gene can be targeted for knock-out or activation in a cell type selective manner Drosophila also offers the advantage that its brain i composed of a relatively small number of stereotyped neuronal lineages, groups of neurons descended from individual embryonic stem cells, called neuroblasts. During the course of its proliferation, each neuroblast expresses characteristic sets of regulatory genes. These genes control the differentiation of the neurons born from that particular neuroblast during a particular time interval. Through this mechanism, a lineage, or smaller subdivision of a lineage called sublineage, develops into a specific class of neurons which share common wiring properties, including the projection of their axons, branching pattern, and placement of synapses. Several discrete neuronal classes/lineages are put together into a neuronal circuit. We have identified a circuit, called the anterior visual pathway (AVP), which conducts input form the eye to a brain center, the central complex, known to process and store visual information in order to control fly locomotion (walking, flight). The central part of this circuit is formed by three lineages, whose neurons form several classes of highly ordered parallel and sequential elements. In our first aim we will investigate the function of the neuronal classes of the AVP, by recording their activity in response to defined visual stimuli. We will also demonstrate experimentally that these classes of neurons are directly connected by synapses. The second aim addresses the question how the developmental history of a neuron (time of birth, placement within the spatial framework of the developing brain) relates to its later connectivity within the AVP circuit. Furthermore, by genetically ablating specific classes of AVP neurons and monitoring the response of their normal synaptic partners, we will obtain important clues towards the role of specific cell interactions ordering connectivity. Thirdly, using high throughput RNAseq, we will analyze the complete assortment of genes (transcriptome) expressed differentially in two particular AVP sublineages, R3 and R2. These two classes are distinguished from each other by very few structural criteria, and we will screen for and then analyze genes responsible for their differences in wiring. We expect to identify genes which play a general role in controlling pathway choices and connectivity in the nervous system.

描述（由申请人提供）：本申请的研究询问基因表达如何控制神经元连接，从而控制大脑功能。如果一个人想要理解并（治疗性地）操纵大脑回路，那么这个问题就具有普遍重要性。我们使用果蝇模型系统，其中几乎每个基因都可以以细胞类型选择性方式进行敲除或激活。果蝇还具有这样的优势：其大脑由相对少量的定型神经元谱系组成，这些神经元群源自单个胚胎干细胞，称为神经母细胞。在其增殖过程中，每个神经母细胞都会表达一组特征性的调节基因。这些基因控制特定神经母细胞在特定时期产生的神经元的分化。时间间隔。通过这种机制，谱系或谱系的较小细分（称为亚谱系）发展成特定类别的神经元，它们具有共同的布线特性，包括轴突的投影、分支模式和突触的位置。几个离散的神经元类别/谱系被组合成一个神经元回路。我们已经确定了一个称为前视觉通路（AVP）的电路，它将来自眼睛的输入传导到大脑中心，即中央复合体，已知处理和存储视觉信息以控制苍蝇运动（行走、飞行）。该电路的中心部分由三个谱系形成，其神经元形成几类高度有序的并行和顺序元件。在我们的第一个目标中，我们将通过记录 AVP 神经元类别的活动来研究它们的功能对特定视觉刺激的反应。我们还将通过实验证明这些类别的神经元是通过突触直接连接的。第二个目标解决神经元的发育历史（出生时间、发育中大脑空间框架内的位置）如何与其后来在 AVP 回路内的连接相关的问题。此外，通过基因消融特定类别的 AVP 神经元并监测其正常突触伙伴的反应，我们将获得关于特定细胞相互作用排序连接的作用的重要线索。第三，使用高通量 RNAseq，我们将分析在两个特定 AVP 亚系 R3 和 R2 中差异表达的完整基因（转录组）。这两个类别通过很少的结构标准相互区分，我们将筛选并分析导致它们接线差异的基因。我们期望找到在控制神经系统通路选择和连接方面发挥一般作用的基因。