Molecular mechanisms regulating chemosensory cilia organization

调节化学感应纤毛组织的分子机制

• 批准号: 10387647
• 负责人: Hannah N Lawson
• 金额: $ 4.16万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-03-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10387647
• 关键词: Ablation; Address; Adhesions; Affect; Afferent Neurons; Altered Taste; Aman; Animals; Anosmia; Area; Behavior; Bilateral; Biology; Caenorhabditis elegans; Calcium; Candidate Disease Gene; Cell Communication; Cells; Chemicals; Cilia; Code; Communication; Defect; Environment; Event; Foundations; Functional disorder; G-Protein-Coupled Receptors; Genetic Screening; Glycoproteins; Goals; Head; Image; Inosine Dialdehyde; Knowledge; Laboratory Organism; Link; Mannosidase; Mediator of activation protein; Mentorship; Microscopy; Modeling; Molecular; Monitor; Mus; Mutation; Nasal Epithelium; Nematoda; Neuroglia; Neurons; Neuropil; Olfactory Epithelium; Organ; Organelles; Organism; Pattern; Pheromone; Positioning Attribute; Process; Property; Protein Tyrosine Phosphatase; Reporter; Research; Research Personnel; Resolution; Role; Sense Organs; Sensory; Shapes; Signal Transduction; Signaling Molecule; Signaling Protein; Smell Perception; Stimulus; Structure; System; Testing; Tissues; Training; Vesicle; Work; base; behavioral response; experimental study; extracellular vesicles; fitness; genetic manipulation; hearing impairment; mutant; olfactory sensory neurons; protein function; protein transport; receptor; response; skills; social; uptake; vesicular release

Project Summary Communication between animals relies on sensory reception, transduction, and processing. Loss of hearing, smell or taste alters social as well as environmental interactions, and adversely affects animal survival and fitness. Primary cilia are present on all sensory neurons, including on olfactory neurons in the vertebrate nasal epithelium. These cilia house all olfactory signaling molecules and are thus critical for sensory reception. The organization of neurons and their processes within neuropils is known to be important for neuron function, but the organization of cilia within sense organs is poorly studied. In the mouse olfactory epithelium, olfactory sensory neurons (OSNs) in highly stimulated regions contain longer cilia, suggesting that ciliary patterns may have functional consequences. The cilia of eight chemosensory neurons of the C. elegans bilateral amphid sense organs are present within a channel formed by surrounding glia. These cilia are stereotypically arranged, giving rise to specific cilia-cilia contacts. The functions of each of these chemosensory neurons are known and can be readily assessed via imaging of stimulus-evoked behaviors and intracellular calcium dynamics. Thus, this system provides an excellent model in which to study cilia organization and its impact on chemosensory neuron functions. This proposal will investigate the molecular mechanism controlling cilia organization in a sense organ, and whether this organization or the cilia-cilia contacts that arise from it, influence chemosensory neuron functions. The results from this work will provide foundational knowledge about cilia organization and its importance in chemosensory neuron function, a largely unexplored area of chemosensory biology. The experiments described in this proposal will provide training in high-resolution microscopy and quantitative analyses of chemosensory behaviors and neuronal responses. Additionally, this proposal includes specific plans to enhance training in mentorship, scientific communication, and networking, all of which are critical skills to become an independent researcher.

项目摘要 动物之间的交流依赖于感觉接受，转导和加工。听力丧失， 气味或味道改变社交和环境互动，并对动物的生存产生不利影响 健康。所有感觉神经元中都存在原发性纤毛，包括脊椎动物鼻嗅神经元上 上皮。这些纤毛室所有嗅觉信号分子，因此对于感觉接受至关重要。这 神经元的组织及其在神经膜中的过程对于神经元功能很重要，但是 在有感觉器官中的纤毛组织的组织很少。在小鼠嗅觉上皮中，嗅觉 高度刺激区域中的感觉神经元（OSN）含有更长的纤毛，表明睫状模式可能 具有功能后果。秀丽隐杆线虫双侧两栖动物的八个化学感应神经元的纤毛 在周围神经胶质形成的通道中存在感官器官。这些纤毛是刻板印象的 布置，引起了特定的纤毛 - 西里亚接触。这些化学感应神经元中每个功能的功能是 已知，可以通过刺激诱发的行为和细胞内钙的成像来评估 动力学。因此，该系统提供了研究纤毛组织及其对影响的出色模型 化学感应神经元功能。该建议将研究控制纤毛的分子机制 在某种意义上的器官中，该组织还是由此产生的纤毛 - 西里亚联系， 影响化学感应神经元功能。这项工作的结果将提供基本知识 关于纤毛组织及其在化学感应神经元功能中的重要性，这是一个很大程度上未开发的领域 化学感应生物学。本提案中描述的实验将提供高分辨率的培训 显微镜和化学感应行为和神经元反应的定量分析。另外，这个 建议包括增强指导，科学沟通和网络培训的具体计划， 所有这些都是成为独立研究人员的关键技能。