Genetics of neural precursor communication during development of the Drosophila peripheral nervous system

果蝇周围神经系统发育过程中神经前体通讯的遗传学

• 批准号: 10573914
• 负责人: Ginger Loraine Hunter
• 金额: $ 13.73万
• 依托单位: CLARKSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10573914
• 关键词: 3-Dimensional; Actins; Adult; Affect; Animal Behavior; Apoptosis; Behavior; Behavioral Assay; Biological Models; Bipolar Neuron; Candidate Disease Gene; Caspase; Cell Communication; Cell Cycle; Cell Cycle Progression; Cell division; Cells; Chest; Communication; Complex; Confocal Microscopy; Data; Defect; Development; Diffuse; Disease; Dorsal; Drosophila genus; Drosophila melanogaster; Environment; Epithelial; Epithelial Cells; Exhibits; Filopodia; Genes; Genetic; Goals; Health; Human; Lateral; Lead; Ligands; Location; Mediating; Microscopy; Modeling; Molecular; Neuraxis; Organ; Organism; Pattern; Peripheral Nervous System; Play; Positioning Attribute; Process; Publishing; Pupa; Quantitative Microscopy; RNA interference screen; Research; Research Personnel; Role; Sensory; Signal Pathway; Signal Transduction; Stimulus; System; Testing; Time; Tissues; Work; base; behavioral outcome; behavioral response; cell behavior; cell type; fly; gene induction; innovation; insight; intercellular communication; knock-down; nerve stem cell; nervous system development; neurogenesis; neuromechanism; notch protein; novel strategies; precursor cell; prevent; relating to nervous system; response; scaffold; stem cell homeostasis; transcription factor

Genetics of neural precursor communication during development of the Drosophila peripheral nervous system The long-term goal of this research is to understand how cell-cell signaling mechanisms drive the organization of the developing peripheral nervous system (PNS). The incorrect spatial and temporal induction of genes and cell behaviors by perturbed signaling can lead to catastrophic errors in an organism’s ability to sense and respond to environmental stimuli. A model system for studying PNS development is the patterning of mechanosensory bristles on the dorsal thorax of the fruit fly Drosophila melanogaster. The developing thoracic PNS undergoes pattern refinement, or the improvement of an initally disordered pattern with time. At least three behaviors of neural precursor cells contribute to pattern refinement, including cell fate switching, adjusting the timing of cell cycle progression, and programmed cell death. The behavioral outcomes that contribute to pattern refinement rely on communication between neural precursor cells, although the mechanisms by which the cells communicate are not known. In Aim 1, a targeted RNAi screen will be performed to test for genes involved in precursor cell communication. The use of Drosophila genetics, adult behavioral assays, and quantitative microscopy will identify candidate genes whose knockdown leads to changes in the pattern refinement process. In Aim 2, an ex vivo strategy will be developed in order to manipulate neural precursor interactions. This novel approach using synthetic 3D scaffolds will test the hypothesis that signaling filopodia (cytoneme) mediated contact is required for neural precursor communication during pattern refinement. Altogether, the innovation of the proposed research lies in its dual approach of identifying both genetic and physical requirements of neural precursor cell-cell communication during pattern refinement. The proposed work is significant because it is expected to uncover conserved mechanisms of cell-cell communication that can be used to target, manipulate, and study neurogenesis and patterning across model systems.

发育过程中神经前体通讯的遗传学 果蝇周围神经系统 这项研究的长期目标是了解细胞-细胞信号机制如何驱动 周围神经系统（PNS）的发育。错误的空间和 通过干扰信号传导对基因和细胞行为的暂时诱导可导致灾难性的 生物体感知和响应环境刺激的能力的错误。一个模型系统 研究PNS发育的最好方法是在胸背上形成机械感觉刚毛的图案 果蝇Drosophila melanogaster。发育中的胸部PNS经历了模式 精细化，或随着时间的推移对初始无序模式的改进。至少三 神经前体细胞的行为有助于模式细化，包括细胞命运转换， 调节细胞周期进程的时间和程序性细胞死亡。行为 有助于模式细化的结果依赖于神经前体之间的通信， 细胞，尽管细胞通信的机制尚不清楚。在目标1中，a 将进行靶向RNAi筛选，以测试参与前体细胞的基因， 通信利用果蝇遗传学、成虫行为测定和定量 显微镜将确定候选基因的敲低导致模式的变化， 精炼过程。在目标2中，将开发一种离体策略，以操纵 神经前体相互作用这种使用合成3D支架的新方法将测试 神经前体需要信号传导丝状伪足（细胞丝）介导的接触的假说 在模式细化期间进行通信。总之，本文的创新之处在于 在于它的双重方法，即确定神经系统的遗传和生理要求， 前体细胞-细胞通信期间的图案细化。拟议的工作意义重大 因为它有望揭示细胞间通讯的保守机制， 用于靶向、操纵和研究跨模型系统的神经发生和模式。