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: 10064625
• 负责人: Shawn Xu
• 金额: $ 37.27万
• 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/10064625
• 关键词: Affect; Animal Behavior; Behavior; Behavioral; Biological Models; Biology; Blood Pressure; Caenorhabditis elegans; Calcium; Cells; Cellular Mechanotransduction; 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; Play; Prevalence; Proprioception; Research; Role; Sensory; Sensory Receptors; Stimulus; Stretching; Study models; System; Testing; Time; Touch sensation; Transfection; Work; behavioral response; blood pressure regulation; bone; cell type; epithelial Na+ channel; hearing impairment; insight; interdisciplinary approach; mechanical force; mechanotransduction; mutant; nervous system disorder; neuromechanism; novel; painful neuropathy; relating to nervous system; 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、触觉、拉伸和重力，激活介导的机械感觉神经元