Neural and genetic mechanisms underlying mechanosensation in C. elegans

机械刺激，如声音、触觉、伸展和重力，激活机械感觉神经元 机械感觉方式，如听力、本体感觉、触摸和血压调节。中环 机械感觉中的参与者是机械传递通道，它检测机械力和 把它们转换成电输出。值得注意的是，除了神经元之外，许多其他类型的细胞，如 骨骼、肌肉、肾脏和眼睛中的那些也会对各种机械刺激做出反应。尽管盛行 在机械转导通道中，在哺乳动物中几乎没有发现这样的通道。显然，小说 哺乳动物中必须存在机械转导通道的类型，但仍有待鉴定。特别是， 哺乳动物中介导听力的机械转导通道的分子特性尚不清楚。 而且极具争议性。新战略和新模式系统的发展可能会促进 新型机械转导通道的鉴定。线虫代表了一种有价值的遗传模型 用于研究感觉生物学。为了在恶劣的环境中生存和茁壮成长，蠕虫进化出了丰富的 一系列感官系统，使它们能够感知气味、味觉、触觉和光线，并对其做出反应，覆盖四个 在五种主要的感觉模式中。更重要的是，编码感官受体和 渠道往往是进化保守的蠕虫。这一点，加上其生成时间较短(~3天) 和方便的遗传工具，使线虫成为识别新的感觉受体和 频道。然而，蠕虫被认为对声音不敏感。在这里，我们建议开发线虫 作为研究声音感觉以及潜在的神经和遗传机制的新模型。要做到这一点， 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进化上趋于保守，所以在C。 这项拟议的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，因为许多类型的细胞是机械敏感的，但只有少数机械转导 渠道已经克隆，建议的工作也将有助于小说的鉴定 调节其他机械感觉方式(如触摸、本体感觉、血液)的机械转导通道 压力调节等)在哺乳动物身上。

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.