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，例如声音、触摸、拉伸和重力，会激活介导的机械感觉神经元 机械感觉模式，例如听觉、本体感觉、触觉和血压调节。中央 机械感觉的参与者是检测机械力和机械力传导通道 将它们转换成电输出。值得注意的是，除了神经元之外，许多其他细胞类型，例如 骨骼、肌肉、肾脏和眼睛中的神经元也对各种机械刺激做出反应。尽管流行 尽管存在机械转导通道，但在哺乳动物中很少发现这样的通道。貌似小说 哺乳动物中必定存在机械转导通道的类型，但仍有待鉴定。尤其， 介导哺乳动物听力的机械传导通道的分子身份仍然不清楚 并且极具争议性。新战略、新模式体系的制定可能会促进 识别新型机械传导通道。线虫代表了一种有价值的遗传模型 用于感觉生物学的研究。为了在恶劣的环境中生存和繁衍，蠕虫进化出了丰富的 使它们能够感知气味、促味剂、触觉和光并做出反应的感觉系统库，涵盖四个 五种主要感觉方式中的一种。更重要的是，编码感觉受体和 蠕虫的通道在进化上往往是保守的。这一点，加上它的生成时间短（约 3 天） 和简便的遗传工具，使秀丽隐杆线虫成为识别新型感觉受体和 渠道。然而，蠕虫被认为对声音不敏感。在这里，我们建议开发秀丽隐杆线虫 作为研究声音感觉及其潜在神经和遗传机制的新模型。为此， 我们将采取多学科方法，结合分子遗传学、行为分析、功能分析 成像和电生理学。由于感觉受体和通道在 C 中往往是进化保守的。 线虫，拟议的工作将为我们对哺乳动物声音感觉的理解提供新的见解。 从更广泛的角度来看，由于许多细胞类型是机械敏感的，但只有少数细胞类型具有机械转导作用 渠道已经被克隆，拟议的工作也将有助于识别新的 介导其他机械感觉模式（例如触摸、本体感觉、血液 压力调节等）在哺乳动物中。