How do discriminative touch receptors selectively innervate peripheral targets?

辨别性触觉感受器如何选择性地支配外周目标？

• 批准号: 9312899
• 负责人: Blair Addison Jenkins
• 金额: $ 4.9万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9312899
• 关键词: Address; Adult; Afferent Neurons; Allografting; Amyloid beta-Protein; Antibodies; Appearance; Area; Artificial skin; Axon; Behavior; Biological Assay; Cells; Coculture Techniques; Complex; Cues; Cutaneous; Dermal; Development; Developmental Process; Embryo; Embryonic Development; Environment; Epidermis; Epithelial; Epithelium; Fibroblasts; Future; Genetic Models; Goals; In Vitro; Investigation; Knowledge; Label; Mediating; Merkel Cells; Mesenchymal; Molecular; Morphology; Mus; Neurites; Neuroglia; Neurons; Organ; Pattern; Peripheral; Population; Process; Recruitment Activity; Reporter; Research; Role; Sensory; Shapes; Site; Skin; Specialized Epithelial Cell; Specific qualifier value; Spinal Ganglia; Stem cells; Sterile coverings; Stimulus; Structure; Tactile; Techniques; Testing; Touch sensation; Transgenic Mice; Transgenic Organisms; Vibrissae; appendage; bone morphogenetic protein 4; cell type; cognitive development; feeding; in vivo; insight; nerve supply; nervous system development; neuron development; novel; object shape; public health relevance; receptive field; receptor; selective expression; skin allograft; somatosensory; spatiotemporal

 DESCRIPTION (provided by applicant): The importance of touch is undeniable: it is an essential sense for our survival that allows us to navigate the physical world. It is vital not onl for simple daily activities such as feeding and dressing, but also for appropriate cognitive development. The long-term goal of this research is to analyze the basic developmental mechanisms mechanisms that mediate proper somatosensory innervation of target skin structures. The objective of this application is to identify the role of peripheral target cell populations in the recruitment of Merkel-cell afferents to specialized sensory domains. Merkel cells together with cutaneous sensory afferents form gentle-touch receptors that are important for encoding shapes, edges, and curvature. These touch receptors are enriched in skin areas that mediate discriminative touch sensation, including fingertips and whisker follicles. Though Merkel cells are innervated by Aß afferents, these cells are not required for directing Aß afferents to Merkel-cell-enriched skin areas during development. This application's central hypothesis is that specialized cell types that are juxtaposed to Merkel cells during development are responsible for the recruitment of Merkel-cell afferents. Aim 1 will analyze the spatiotemporal dynamics of the appearance of these cells relative to the innervation of Merkel-cell afferents in high-acuity skin areas. I will use transgenic fluorescent reporter mice and antibodies against cell-type specific markers to label these components. Aim 2 will test whether these cell types are sufficient to recruit Merkel-cell afferents both in vivo and in vitro. These studies will define the mechanisms that drive guidance of afferents to their targets and will enhance our understanding of how body sites are specialized for distinct somatosensory functions.

 描述（由申请人提供）：触摸的重要性是不可否认的：它是我们生存的基本感觉，使我们能够驾驭物质世界。它不仅对于喂养和穿衣等简单的日常活动至关重要，而且对于适当的认知发展也至关重要。这项研究的长期目标是分析介导目标皮肤结构适当体感神经支配的基本发育机制。该应用的目的是确定外周靶细胞群在将默克尔细胞传入神经募集到专门的感觉域中的作用。默克尔细胞与皮肤感觉传入细胞一起形成轻柔的触觉感受器，这对于编码形状、边缘和曲率非常重要。这些触觉感受器富含于介导辨别性触觉的皮肤区域，包括指尖和胡须毛囊。尽管默克尔细胞受 Aß 传入神经支配，但在发育过程中，这些细胞不需要将 Aß 传入神经引导至富含默克尔细胞的皮肤区域。该应用的中心假设是，在发育过程中与默克尔细胞并列的特殊细胞类型负责招募默克尔细胞传入神经。目标 1 将分析这些细胞的外观相对于高敏锐度皮肤区域默克尔细胞传入神经支配的时空动态。我将使用转基因荧光报告小鼠和针对细胞类型特异性标记的抗体来标记这些成分。目标 2 将测试这些细胞类型是否足以在体内和体外招募默克尔细胞传入细胞。这些研究将定义驱动传入神经引导至目标的机制，并将增强我们对身体部位如何专门用于不同体感功能的理解。