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（通过应用程序提供）：该应用的研究询问基因表达如何控制神经元连接性，从而如何控制大脑功能。如果要理解并（治疗）操纵脑电路，这个问题至关重要。我们使用模型系统果蝇，几乎可以将每个基因以细胞类型的选择性方式敲除或激活果蝇，还提供了一个优势：它的大脑I由相关的少量刻板神经元谱系组成，神经元的群体是从单个胚胎干细胞中降低的神经元，称为神经细胞。在增殖过程中，每个神经细胞都表达了调节基因的特征集。这些基因控制了特定的特定神经细胞的神经元的分化时间间隔。通过这种机制，称为sublineage的谱系的血统或较小的细分发展为具有共同的共同接线特性的特定神经元，包括其轴突的投影，分支模式和突触的放置。将几个离散的神经元类/谱系放在神经元电路中。我们已经确定了一个称为前视觉途径（AVP）的电路，该电路将输入形成眼睛到大脑中心，该中心是中央综合体，已知可以处理和存储视觉信息以控制飞行运动（步行，飞行）。该电路的中心部分由三个谱系形成，其神经元形成了几类高度有序的平行和顺序元素。在我们的第一个目标中，我们将通过记录其活动在对定义的视觉刺激的响应。我们还将通过实验证明这些类别的神经元通过突触直接连接。第二个目的解决了一个问题，即神经元的发育历史（出生时间，在发育大脑的空间框架内的放置）如何与AVP电路中的后来连通性有关。此外，通过遗传消除特定类别的AVP神经元和监测其正常突触伴侣的反应，我们第三使用高吞吐量RNASEQ，我们将分析基因（Transcriptome）的完整分类（转录组）在两个特定的AVP Sublineages，R3和R2中的表达方式不同。这两个类别彼此区分的结构标准很少，我们将筛选并分析负责其接线差异的基因。我们希望确定在控制神经系统中的途径选择和连通性中发挥一般作用的基因。