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官的接收、传导和处理。听力丧失， 气味或味道改变了社会和环境的相互作用，并对动物的生存产生不利影响， 健身初级纤毛存在于所有的感觉神经元上，包括脊椎动物鼻腔中的嗅觉神经元上。 上皮这些纤毛容纳所有嗅觉信号分子，因此对感觉接收至关重要。的 已知神经元及其在神经柱内的过程的组织对于神经元功能是重要的，但是 对感觉器官内纤毛的组织研究很少。在小鼠嗅上皮中， 高度刺激区域的感觉神经元（OSN）含有较长的纤毛，这表明纤毛模式可能 具有功能性后果。用电镜观察了C.秀丽双足类 感觉器官存在于由周围神经胶质形成的通道内。这些纤毛是典型的 排列，引起特定的纤毛纤毛接触。这些化学感受神经元的功能是 已知并且可以通过刺激诱发的行为和细胞内钙的成像容易地评估 动力学因此，该系统提供了一个很好的模型，在其中研究纤毛组织及其影响， 化学感觉神经元功能。本计画将探讨控制纤毛的分子机制 感觉器官中的组织，无论是这个组织还是从它产生的纤毛-纤毛接触， 影响化学感觉神经元功能。这项工作的结果将提供基础知识 关于纤毛组织及其在化学感觉神经元功能中的重要性，这是一个很大程度上尚未探索的领域， 化学感受生物学本提案中描述的实验将提供高分辨率的培训 化学感觉行为和神经元反应的显微镜和定量分析。而且这个 建议包括加强指导、科学交流和联网方面的培训的具体计划， 所有这些都是成为独立研究人员的关键技能。