How do discriminative touch receptors selectively innervate peripheral targets?

 描述(申请人提供)：触摸的重要性是不可否认的：它是我们生存的一种基本感觉，使我们能够在物质世界中导航。它不仅对于简单的日常活动，如喂食和穿衣，而且对适当的认知发展也是至关重要的。这项研究的长期目标是分析调节靶皮肤结构适当的体感神经支配的基本发育机制。这项应用的目的是确定外周靶细胞群体在默克尔细胞传入到专门感觉领域的招募中所起的作用。默克尔细胞与皮肤感觉传入一起形成了轻柔的感受器，对编码形状、边缘和曲率非常重要。这些触摸感受器富含在皮肤区域，包括指尖和胡须毛囊，这些区域调节有区别的触摸感觉。虽然默克尔细胞由A？传入神经支配，但在发育过程中，这些细胞并不需要将A？传入神经引导到富含默克尔细胞的皮肤区域。这一应用的中心假设是，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。目的1将分析这些细胞的出现与高敏感度皮肤区域Merkel细胞传入神经支配相关的时空动力学。我将使用转基因荧光报告鼠和针对细胞类型特定标记的抗体来标记这些成分。目的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。这些研究将确定将传入引导到其目标的机制，并将加强我们对身体部位如何专用于不同的躯体感觉功能的理解。

 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.