Understanding the Molecular Mechanisms of Neuronal Control in Sweat Gland Development

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PROJECT SUMMARY Eccrine sweat glands are the most abundant gland in our skin and are essential for thermoregulation and skin homeostasis. It was only recently that multipotent stem cells in the sweat glands were identified, which presented great potential for de novo sweat gland regeneration. Further, in order to make sweat glands functional, precise innervation and neuronal control are indispensable. Neuronal signals elicit sweating; but also, are necessary for sweat gland maturation based on prior work in our lab. Sweat glands and neurons rely on each other for proper development; however, very little is known about how neuronal inputs influence sweat gland development, especially the sweat gland stem cells. We hypothesize that neuronal innervation is critical for the maintenance of sweat gland stem cells during development. Using mouse sweat gland as a model, we will investigate the molecular changes in the sweat gland stem cells during development when lacking innervation, and further identify the downstream pathway within sweat gland stem cells that mediates the effect of neurotransmitters upon stem cell maintenance. This proposal aims to i) investigate the effect of neuronal input during sweat gland development ii) understand the role of neurotransmitters in sweat gland development iii) examine whether calcium mediates neuronal control of the sweat gland stem cells. These studies will provide greater insight into how nerves regulate the development and maintenance of sweat glands. Further, this proposal will establish a foundational understanding of how sweat glands and neurons develop into a function unit which will be useful for regenerative therapies.