Neural and genetic mechanisms underlying mechanosensation in C. elegans

秀丽隐杆线虫机械感觉的神经和遗传机制

• 批准号: 10531246
• 负责人: Shawn Xu
• 金额: $ 35.41万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-05 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10531246
• 关键词: Affect; Animal Behavior; Behavior; Behavioral; Biological Models; Biology; Caenorhabditis elegans; Calcium; Cells; Data; Defect; Development; Disease; Drosophila acetylcholine receptor alpha-subunit; Electrophysiology (science); Environment; Esthesia; Eye; Family; Force of Gravity; Frequencies; Functional Imaging; Generations; Genes; Genetic; Genetic Models; Genetic Screening; Goals; Head; Hearing; Human; Kidney; Lead; Light; Mammals; Mechanics; Mediating; Modality; Modeling; Molecular; Molecular Genetics; Muscle; Mutate; Mutation; Neurons; Odors; Organ; Organism; Output; Persons; Piezo ion channels; Play; Prevalence; Proprioception; Reaction; Research; Role; Sensory; Sensory Receptors; Stretching; Study models; System; Testing; Time; Touch sensation; Work; behavioral response; blood pressure control; blood pressure regulation; bone; candidate identification; cell type; epithelial Na+ channel; hearing impairment; insight; interdisciplinary approach; mechanical force; mechanical stimulus; mechanotransduction; mutant; nervous system disorder; neural; neuromechanism; novel; painful neuropathy; response; sensory system; sound; tool

Mechanical stimuli, such as sound, touch, stretch and gravity, activate mechanosensory neurons that mediate mechanosensory modalities such as hearing, proprioception, touch, and blood pressure regulation. The central player in mechanosensation is the mechanotransduction channel that detects mechanical forces and transduces them into electrical outputs. Remarkably, in addition to neurons, many other cell types, such as those in the bone, muscle, kidney and eye, also respond to various mechanical stimuli. Despite the prevalence of mechanotransduction channels, few such channels have been identified in mammals. Apparently, novel types of mechanotransduction channels must be present in mammals but remain to be identified. In particular, the molecular identity of the mechanotransduction channel mediating hearing in mammals remains obscure and highly controversial. The development of new strategies and new model systems may facilitate the identification of novel types of mechanotransduction channels. C. elegans represents a valuable genetic model for the study of sensory biology. To survive and thrive in the harsh environment, worms have evolved a rich repertoire of sensory systems that allow them to sense and react to odor, tastant, touch and light, covering four out of the five primary sensory modalities. More importantly, the genes encoding sensory receptors and channels tend to be evolutionarily conserved in worms. This, together with its short generation time (~3 days) and facile genetic tools, makes C. elegans an ideal system for identifying novel sensory receptors and channels. Nevertheless, worms are considered insensitive to sound. Here, we propose to develop C. elegans as a new model for studying sound sensation and the underlying neural and genetic mechanisms. To do so, we will take a multidisciplinary approach combining molecular genetics, behavioral analysis, functional imaging, and electrophysiology. As sensory receptors and channels tend to be evolutionarily conserved in C. elegans, the proposed work will provide novel insights into our understanding of sound sensation in mammals. On a broader perspective, as many cell types are mechanosensitive, yet only a few mechanotransduction channels have been cloned, the proposed work will also facilitate the identification of novel mechanotransduction channels mediating other mechanosensory modalities (e.g. touch, proprioception, blood pressure regulation, etc.) in mammals.

机械刺激，如声音，触摸，拉伸和重力，激活机械感觉神经元， 机械感觉形式，如听觉、本体感觉、触觉和血压调节。中央 机械感觉中的参与者是检测机械力的机械传导通道， 将它们转换成电输出。值得注意的是，除了神经元，许多其他细胞类型，如 骨骼、肌肉、肾脏和眼睛中的神经元也对各种机械刺激作出反应。尽管流行 在机械转导通道中，很少有这样的通道在哺乳动物中被鉴定。显然，小说 机械传导通道的类型必须存在于哺乳动物中，但仍有待鉴定。特别是， 哺乳动物中介导听力的机械传导通道的分子特性仍然不清楚 也极具争议新战略和新模式系统的发展可能会促进 新类型的机械传导通道的鉴定。C.秀丽线虫代表了一种有价值的遗传模型 用于感官生物学的研究。为了在恶劣的环境中生存和繁衍，蠕虫进化出了丰富的 感觉系统的剧目，使他们能够感觉和反应的气味，味觉，触觉和光，涵盖四个 五种主要的感觉方式。更重要的是，编码感觉受体和 通道在蠕虫中趋于进化保守。这一点，加上它的短世代时间（~3天） 和简单的遗传工具，使C。elegans是一个理想的系统，用于识别新的感觉受体， 渠道然而，蠕虫被认为对声音不敏感。在这里，我们建议开发C。elegans 作为研究声音感觉和潜在的神经和遗传机制的新模型。为此， 我们将采取多学科的方法，结合分子遗传学，行为分析，功能 成像和电生理学。由于感觉受体和通道在C. elegans，这项工作将为我们理解哺乳动物的声音感觉提供新的见解。 从更广泛的角度来看，许多细胞类型是机械敏感的，但只有少数机械转导 通道已被克隆，拟议的工作也将促进新的识别 介导其他机械感觉模态（例如，触摸、本体感觉、血液）的机械传导通道 压力调节等）在哺乳动物中。