Determining the Role of Bacterial Products on Neuronal Localization and Function in a Symbiotic Organ

确定细菌产物对共生器官神经元定位和功能的作用

• 批准号: 10647940
• 负责人: Elizabeth A. Heath-Heckman
• 金额: $ 18.78万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10647940
• 关键词: Activities of Daily Living; Address; Adolescent; Affect; Animals; Apoptosis; Bacteria; Biological Models; Biology; Brain; Central Nervous System; Characteristics; Communities; Complex; Data; Development; Embryonic Development; Enteral; Enteric Nervous System; Epithelium; Euprymna scolopes; FMRFamide; Foundations; Genes; Genetic; Goals; Hawaiian; Hindgut; Image; Imaging Techniques; In Situ Hybridization; Individual; Knowledge; Label; Light; Lipopolysaccharides; Location; Mediating; Methods; Microbe; Modeling; Nervous System; Neurobiology; Neuronal Plasticity; Neurons; Neuropeptides; Neurotransmitters; Nitric Oxide; Optics; Organ; Outcome; Pathway interactions; Peptidoglycan; Peripheral Nervous System; Phenotype; Physiology; Positioning Attribute; Postembryonic; Process; Production; Proteins; RNA; Reaction; Resources; Role; Signal Transduction; Source; Squid; Structure; Study models; Surface; Symbiosis; System; Techniques; Testing; Time; Tissues; V. fischeri-squid system; Vibrio; Vibrio fischeri; Visualization; Whole Organism; Work; appendage; beneficial microorganism; connectome; gene product; gut microbiome; hatching; immunocytochemistry; innovation; insight; interest; microbial; microbiome; mutant; mutualism; neurodevelopment; neuron development; pharmacologic; receptor; response; symbiont; transcriptome sequencing

PROJECT SUMMARY Bacteria, such as those found in the vertebrate gut microbiome, have been shown to have widespread effects on both the enteric (ENS) and central nervous systems (CNS) in numerous animals. Reciprocally, the ENS has been shown to have an impact on the progression of microbiome establishment in the gut. However, despite the profound influence of bacteria on neuronal development and physiology, the diversity of the vertebrate gut microbiome and the complexity of the ENS make the mechanisms underlying these phenomena difficult to study. Despite the importance of the topic and vertebrate models, these systems involve microbiomes that are both spatially and compositionally complex, often with thousands of bacterial species that can very between individual hosts. Therefore there is a role for simple, exquisitely manipulable model systems in which to study the effects of bacterial symbionts on neuronal development and function. To address the dearth of such models for the mechanisms by which bacteria influence host neurobiology, we propose to use the symbiosis between the Hawaiian bobtail squid (Euprymna scolopes) and its luminescent bacterial symbiont Vibrio fischeri as a tractable system in which to study how bacteria drive host neuronal development. The squid-vibrio system is a well-established model for the effects of bacterial products on host physiology and development, with outcomes that are often generalizable to other animal systems. This proposal aims to develop the squid-vibrio system into a new model for the study of the effects of microbes on host neurobiology. In our first aim we will define the neuronal landscape of the light organ, including neuronal position and identity and the effect of symbiosis and bacterial products on both. To achieve this aim, we will develop new methods for dual labeling of RNA and proteins in our system and adapt neuronal tracing techniques for imaging in the light organ. In our second aim we propose to study the role of neuropeptide signaling on transducing microbial signals from V. fischeri to tissues on the outside of the symbiotic organ. Specifically, we will determine the location and dynamics of FMRFamide signaling in the light organ over the first three days of symbiosis and will examine the effects of FMRFamide signaling on bacterially-mediated post-embryonic development. The data arising from this proposal will not only lay the foundation for a powerful new model system, but will also generate new resources and techniques for the community and provide new insights as to the role of the peripheral nervous system in potentiating microbially-mediated development.

项目概要 细菌，例如在脊椎动物肠道微生物组中发现的细菌，已被证明具有广泛的传播性 对许多动物的肠道（ENS）和中枢神经系统（CNS）都有影响。反过来， ENS 已被证明对肠道微生物组建立的进展有影响。然而， 尽管细菌对神经元发育和生理学有着深远的影响，但细菌的多样性 脊椎动物肠道微生物组和 ENS 的复杂性构成了这些现象背后的机制 很难学习。尽管主题和脊椎动物模型很重要，但这些系统涉及 微生物组在空间和组成上都很复杂，通常有数千种细菌 各个主机之间可以非常。因此，简单、可精细操作的模型系统发挥着重要作用 研究细菌共生体对神经元发育和功能的影响。为了解决 由于缺乏细菌影响宿主神经生物学机制的模型，我们建议使用 夏威夷短尾乌贼（Euprymna scolopes）与其发光细菌共生体之间的共生关系 费氏弧菌作为一个易于处理的系统，用于研究细菌如何驱动宿主神经元发育。这 鱿鱼-弧菌系统是细菌产物对宿主生理学影响的成熟模型。 的发展，其结果通常可以推广到其他动物系统。该提案旨在 将鱿鱼-弧菌系统开发为研究微生物对宿主神经生物学影响的新模型。 在我们的第一个目标中，我们将定义光器官的神经元景观，包括神经元位置和身份 以及共生和细菌产物对两者的影响。为了实现这一目标，我们将开发新方法 用于在我们的系统中对 RNA 和蛋白质进行双重标记，并采用神经元追踪技术进行成像 光器官。在我们的第二个目标中，我们建议研究神经肽信号转导微生物的作用 费氏弧菌向共生器官外部​​的组织发出信号。具体来说，我们将确定 共生前三天 FMRFamide 信号在光器官中的位置和动态，并将 检查 FMRFamide 信号对细菌介导的胚胎后发育的影响。数据 该提案的产生不仅将为强大的新模型系统奠定基础，而且还将 为社区创造新的资源和技术，并就社区的作用提供新的见解 周围神经系统增强微生物介导的发育。