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？

基本信息

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
项目类别：
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

项目摘要

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（由适用提供）：触摸的重要性是不可否认的：对于我们的生存而言，这是一个必不可少的感觉，它使我们能够驾驭物理世界。对于简单的日常活动，例如喂养和敷料，而是适当的认知发展，这一点至关重要。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的基本发展机制。该应用的目的是确定外围靶细胞种群在将默克尔细胞传入募集到专门的感觉域中的作用。默克尔细胞与皮肤的感觉传入形成柔和的受体，对于编码形状，边缘和曲率很重要。这些触摸受体富含在介导判断性触摸感的皮肤区域，包括指尖和晶须卵泡。尽管Merkel细胞由Aß传入支配，但这些细胞在发育过程中指导Aß传入到富含默克尔细胞的皮肤区域并不需要这些细胞。该应用程序的中心假设是，在开发过程中与默克尔细胞并列的专门细胞类型负责募集默克尔细胞传入。 AIM 1将分析这些细胞外观的时空动力学相对于高力皮肤区域中Merkel-Cell传入的神经支配。我将使用转基因荧光记者小鼠和针对细胞类型特异性标记的抗体来标记这些成分。 AIM 2将测试这些细胞类型是否足以在体内和体外募集默克尔细胞传入。这些研究将定义将传入引导到其目标的机制，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。