Lineage-associated wiring properties of Drosphila brain neurons

果蝇脑神经元的谱系相关布线特性

基本信息

批准号：
9310358
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：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9310358
关键词：
Address Adult Alpha Cell Anatomy Animals Anterior Axon Behavior Biological Neural Networks Brain Cell Lineage Cells Characteristics Collection Complement Complex Cues Data Data Set Date of birth Defect Development Disease Drosophila genus Electrons Embryo Funding Gene Expression Gene Expression Profile Genes Genetic Genetic Identity Genetic study Goals Grant Grouping Health Human Image Individual Invertebrates Knock-out Knowledge Label Learning Length Link Lobe Location Maps Measurable Memory Microscopic Mushroom Bodies Nerve Fibers Nervous system structure Neurites Neurons Output Pathway interactions Pattern Play Process Property Research Resolution Role Semaphorins Series Shapes Site Sorting - Cell Movement Stem cells Stereotyping Structure Surface Synapses Techniques To specify Vertebrates Work base brain circuitry cell type design developmental genetics experimental analysis fly genetic analysis loss of function mutation migration mind control molecular marker mutant neuroblast neurogenetics neuromuscular system neuronal circuitry overexpression postsynaptic progenitor public health relevance reconstruction screening sensory system software development three-dimensional modeling time interval tool transcription factor virtual

项目摘要

DESCRIPTION (provided by applicant): Brain function is based upon the precise connectivity of a large number of neurons. Connectivity in turn depends in large part on the genetically determined wiring properties of neurons, including their neurite projection, branching, and placement of synaptic contacts with specific partners. To understand and manipulate brain circuits one needs a detailed knowledge of how the genes expressed in a developing neuron control the wiring properties of this cell. For genetic studies, Drosophila offers many advantages, in that virtually every gene can be targeted for knock-out or activation in a cell type selective manner. More importantly in the context of studying neuronal circuitry, the Drosophila brain is composed of a manageable number of stereotyped neuronal lineages, groups of neurons descended from individual stem cells (neuroblasts) born in the embryo. During the course of its proliferation, each neuroblast expresses characteristic sets of genes (transcription factors) which are thought to specify the wiring properties of the neurons born from that particular neuroblast during a particular time interval. These neurons form a so called sublineage. To learn about the genetic control of brain circuitry we and others have taken the approach to document the structural properties of lineages and sublineages, and correlate them to the dynamic pattern of gene expression in the neuroblast. During the previous funding period we have generated detailed maps and 3D models of all lineages constituting the adult and larval brain. We here propose three aims that continue and extend this work. First, we will reconstruct the connectivity of a subset of larval brain lineages and their sublineages that form a particular, well characterized circuit. This reconstruction will be done at a so far unparalleled level of resolution, using a series of several thousand contiguous electron microscopic sections in conjunction with a specially developed software package that allows us to assign all synapses to specific neurons and their lineages. Secondly, we will link the structurally defined lineages mapped in the larval brain with the neuroblasts of the embryo, using a technique that systematically labels all transcription factors expressed in neuroblasts and then follows the expression of these genes from neuroblast to lineage. Thirdly, we will screen for and genetically characterize genes that play a role in directing lineages to their proper place in a circuit.

描述（由申请人提供）：大脑功能基于大量神经元的精确连接，而连接性在很大程度上取决于神经元的遗传决定的接线特性，包括它们的神经突投射、分支和突触接触的位置。为了理解和操纵大脑回路，我们需要详细了解发育中的神经元中表达的基因如何控制该细胞的布线特性，对于遗传研究来说，果蝇具有许多优势，因为几乎每个基因都可以作为目标。细胞类型的敲除或激活更重要的是，在研究神经元回路的背景下，果蝇大脑由可管理数量的定型神经元谱系组成，这些神经元群是在胚胎增殖过程中产生的单个干细胞（神经母细胞）的后代。每个神经母细胞都表达一组特征基因（转录因子），这些基因被认为指定了在特定时间间隔内从该特定神经母细胞产生的神经元的布线特性，这些神经元形成了所谓的亚谱系。为了控制大脑回路，我们和其他人采用了这种方法来记录谱系和亚谱系的结构特性，并将它们与神经母细胞中基因表达的动态模式相关联。在之前的资助期间，我们已经生成了所有谱系和亚谱系的详细图谱和 3D 模型。我们在这里提出了继续和扩展这项工作的三个目标，首先，我们将重建形成特定的幼虫大脑谱系及其子谱系的连接性。这种重建将以迄今为止无与伦比的分辨率水平进行，使用数千个连续的电子显微镜切片与专门开发的软件包，使我们能够将所有突触分配给特定的神经元及其谱系。，我们将使用一种技术将幼虫大脑中绘制的结构定义的谱系与胚胎标签的神经母细胞联系起来，该技术系统地表达神经母细胞中的所有转录因子，然后跟踪神经母细胞中这些基因的表达第三，我们将筛选和遗传表征在引导谱系到达其在回路中的适当位置方面发挥作用的基因。