PROJECT SUMMARY/ABSTRACT Organ development and function requires that neurons establish precise cellular interactions with tissueresident support cells. For example, touchsensing somatosensory neurons project peripheral axons to the skin, where they interact with specialized skin cell types. These specialized skin cells regulate axon development and modu late neuronal responses to cutaneous stimuli. Reciprocally, somatosensory neurons influence skin homeostasis. Although the anatomy of vertebrate skin is well described, little is known about the dynamic process of sensory specialization of the skin, partly because most studies have focused on mammalian embryos, which has limited access to liveimaging. The external development and the availability of unique transgenic tools make zebrafish an ideal model for study ing the dynamics of neuron and tissue maturation. This proposal investigates the development of a novel popula tion of specialized sensory cells that we identified in the zebrafish epidermis. Preliminary cellular, molecular and developmental analyses suggest that these zebrafish epidermal cells are the equivalent of mammalian Merkel cells, specialized mechanosensory cells that detect touch. The experiments proposed here investigate how de velopment of these specialized epidermal cells is coordinated with skin and nervous system maturation. In Aim 1, we will use liveimaging and genetic manipulation to characterize how sensory cell addition occurs during skin growth. Aim 2 investigates the establishment of interactions between axons and epidermal cells and how neurons promote skin specialization. Finally, in Aim 3, we will use in vivo photoconversion, lineage tracing and molecular techniques to track the trajectory of skinresident stem cells as they differentiate into sensory cells. Collectively, these studies will provide mechanistic insights into organ specialization during development, interactions between peripheral axons and their target tissues, and potentially point to the origins of touchsensing disorders.