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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，从而控制脑功能。这个问题是普遍的重要性，如果一个人想了解，并（治疗）操纵大脑回路。我们使用果蝇的模型系统，其中几乎每个基因都可以以细胞类型选择性方式被靶向敲除或激活。果蝇还提供了其大脑由相对少量的定型神经元谱系组成的优势，这些神经元谱系是由单个胚胎干细胞（称为成神经细胞）遗传而来的神经元组。在其增殖过程中，每一个神经母细胞表达的调控基因的特征集。这些基因控制着神经元的分化，这些神经元是在特定的时间段内从特定的神经母细胞中产生的。时间间隔通过这种机制，一个谱系，或一个谱系的更小的细分称为亚谱系，发展成一类特定的神经元，这些神经元具有共同的布线特性，包括轴突的投射，分支模式和突触的放置。几个离散的神经元类/谱系被放在一起成为一个神经元回路。我们已经确定了一个电路，称为前视觉通路（AVP），它将输入从眼睛传导到大脑中心，即中央复合体，已知用于处理和存储视觉信息以控制苍蝇运动（行走，飞行）。这个回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神经元类的活动来研究AVP神经元类的功能。对特定视觉刺激的反应。我们还将通过实验证明，这些神经元类别是由突触直接连接的。第二个目标是解决一个神经元的发育历史（出生时间，在发育中的大脑的空间框架内的位置）如何与其后来在AVP回路内的连接性相关的问题。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，我们将获得重要的线索，对特定的细胞相互作用有序连接的作用。第三，使用高通量RNAseq，我们将分析在两个特定AVP亚系R3和R2中差异表达的基因（转录组）的完整分类。这两个类别之间的区别在于很少的结构标准，我们将筛选并分析负责它们布线差异的基因。我们希望能够鉴定出在控制神经系统中通路选择和连接方面发挥一般作用的基因。