Genomic Bases of Evolution of Homologous Neurons & Neuronal Circuits

同源神经元进化的基因组基础

• 批准号: 0744649
• 负责人: Leonid Moroz
• 金额: $ 26万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0744649&HistoricalAwards=false
• 关键词: Genomic; Bases; Evolution; Homologous; Neurons

This research will illuminate one of the most challenging aspects of the evolution of neuronal circuits: genomic mechanisms underlying cell-specific adaptive modifications and the origin of novel behaviors. The evolutionary approach is less developed in modern neuroscience. However, it is crucial to understand how complex networks and brains are formed or to answer "why" questions (e.g. why different subsets of signal molecules were selected in distinct neuronal circuits). The evolution of centralized complex brains occurs in parallel, where distinct neural patterning might emerge independently in different lineages but use similar molecular building blocks or toolkits. This project proposes to identify and characterize cellular homologs within defined neural circuitries across opisthobranch species (e.g. Pleurobranchaea and Tritonia) to understand how changes in the genomic organization of homologous neurons lead to adaptive modifications of networks underlying escape and other behaviors. As a result, it will lead to conceptually new approaches when nervous system evolution can be portrayed on an entire genomic scale with single-cell resolution. The hypothesis about whether divergent evolution of neural circuits resulted in the appearance of novel signaling systems and other neuron-specific markers will be tested. Alternatively, novel network properties and connections might emerge as modular rearrangements of preexisting molecular components. Training opportunities for interdisciplinary students will arise during the development of a nation-wide comparative genomic database that will be searchable for neuronal markers and signal transduction pathways. The extensive collection of transcripts will also allow testing evolutionary relationships across neurobiological models with different levels of centralization of their nervous systems. The proposed approaches and methodologies can be generalized to any system and thus will dramatically increase both the information and education opportunities that can be gained from studying classical electrophysiological preparations. The research will provide a long desired marriage of neuroscience and comparative genomics to understand of how specific neuronal networks are organized and evolved.

这项研究将阐明神经元回路进化中最具挑战性的方面之一：细胞特异性适应性修饰背后的基因组机制和新行为的起源。 现代神经科学中的进化方法还不太发达。 然而，了解复杂的网络和大脑是如何形成的或回答“为什么”的问题（例如为什么在不同的神经元回路中选择不同的信号分子子集）至关重要。 集中式复杂大脑的进化是并行发生的，不同的谱系中可能会独立出现不同的神经模式，但使用相似的分子构建块或工具包。该项目旨在识别和表征跨后鳃类物种（例如侧鳃纲和Tritonia）的定义神经回路内的细胞同源物，以了解同源神经元基因组组织的变化如何导致逃避和其他行为背后的网络的适应性修改。 因此，当神经系统进化能够以单细胞分辨率在整个基因组规模上描绘时，它将带来概念上的新方法。 关于神经回路的发散进化是否导致新信号系统和其他神经元特异性标记物出现的假设将得到检验。 或者，新的网络特性和连接可能会作为现有分子组件的模块化重排而出现。 在开发全国范围的比较基因组数据库的过程中，将出现跨学科学生的培训机会，该数据库将可搜索神经元标记和信号转导途径。 大量转录本的收集还将允许测试具有不同神经系统集中程度的神经生物学模型之间的进化关系。 所提出的方法和方法可以推广到任何系统，因此将极大地增加从研究经典电生理学制剂中可以获得的信息和教育机会。 该研究将提供神经科学和比较基因组学的长期期望的结合，以了解特定神经元网络是如何组织和进化的。