How do discriminative touch receptors selectively innervate peripheral targets?

 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，使我们能够在物理世界中导航。它不仅对简单的日常活动（如进食和穿衣）至关重要，而且对适当的认知发展也至关重要。这项研究的长期目标是分析基本的发育机制，调节目标皮肤结构的适当体感神经支配的机制。本申请的目的是确定外周靶细胞群体在Merkel细胞传入到专门的感觉域的募集中的作用。默克尔细胞与皮肤感觉传入一起形成对编码形状、边缘和曲率很重要的轻柔触摸感受器。这些触觉感受器在介导辨别性触觉的皮肤区域中富集，包括指尖和胡须毛囊。虽然默克尔细胞受轴突传入神经支配，但在发育过程中，这些细胞并不需要将轴突传入神经引导到梅克尔细胞富集的皮肤区域。该应用的中心假设是，在发育过程中与默克尔细胞并列的专门细胞类型负责默克尔细胞传入的募集。目的1将分析时空动态的外观，这些细胞相对于神经支配的Merkel细胞传入在高敏度皮肤区域。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Merkel细胞传入。这些研究将确定将传入神经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.