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How do discriminative touch receptors selectively innervate peripheral targets?

$45,047F31FY2016NSNIH

Columbia University Health Sciences, New York NY

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Abstract

? 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.

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