Exploring the evolutionary origins of gene regulatory networks cotrolling neurogenic system development in Drosophila melanogaster

探索控制果蝇神经系统发育的基因调控网络的进化起源

• 批准号: 2432672
• 金额: --
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2432672
• 关键词: Exploring; evolutionary; origins; gene; regulatory

Embryonic neurogenesis requires cell differentiation programmes to be tightly regulated across space and time. Elucidating the spatiotemporal gene expression patterns of the regulatory genes. Involved in neurogenic development is important for understanding how these systems developed. Delineating the transcriptional program underscoring its development should enable us to recapitulate the patterns of embryonic expression that provide an improved view of how these systems function in a wide variety of neuronal functions, including behaviour. This project is developed with the goal to characterise the spatiotemporal combination of transcription factor expression, and the cascade of lineage and time-specific transcription factors that are involved in cell fate specification and differentiation.GRNs are defined as the suite of regulatory genes, along with their regulators, that control transcriptional dynamics within a cell. The project is designed to utilise single-cell sequencing technologies, sampling across critical developmental timepoints of embryonic neuronal development in Drosophila melanogaster, to identify all the molecular players and the temporal patterning of the gene regulatory networks (GRNs) that control the differentiation process for each neuronal subtype. The single-cell data analysis is supplemented with experimental validation using transcript-hybridisation experiments of the transcriptional factors regulating neurogenic development to analyse spatiotemporal organisation. Furthermore, in order to determine causative effect of these regulatory genes, perturbation experiments using CRISPR and RNAi transgenics are performed to analyse the role of each regulatory gene on other genes within its GRN and fundamentally the developmental process of each neuronal subtype. These time-resolved gene expression maps help to establish a high-resolution spatiotemporal profile of the regulatory code underlying neuronal subtype specification and differentiation.

胚胎神经发生需要细胞分化程序在空间和时间上受到严格调控。阐明调控基因的时空基因表达模式。参与神经发育对于理解这些系统是如何发展的是很重要的。描述转录程序强调其发展应该使我们能够概括胚胎表达的模式，提供了一个更好的观点，这些系统如何在各种各样的神经功能，包括行为的功能。本项目的目标是研究转录因子表达的时空组合，以及参与细胞命运指定和分化的谱系和时间特异性转录因子的级联反应。GRNs被定义为一套调控基因，沿着其调节因子，控制细胞内的转录动力学。该项目旨在利用单细胞测序技术，在果蝇胚胎神经元发育的关键发育时间点进行采样，以确定控制每个神经元亚型分化过程的基因调控网络（GRNs）的所有分子参与者和时间模式。单细胞数据分析的补充与实验验证使用转录杂交实验的转录因子调节神经发育分析时空组织。此外，为了确定这些调控基因的致病作用，进行了使用CRISPR和RNAi转基因的干扰实验，以分析每个调控基因对其GRN内其他基因的作用，并从根本上分析每个神经元亚型的发育过程。这些时间分辨的基因表达图谱有助于建立一个高分辨率的时空分布的监管代码的神经元亚型规范和分化。