Understanding the Molecular Mechanisms of Neuronal Control in Sweat Gland Development

项目总结 汗腺是皮肤中含量最丰富的腺体，对体温调节是必不可少的。 和皮肤的动态平衡。直到最近，汗腺中的多能干细胞才被发现， 这为汗腺再生提供了巨大的潜力。此外，为了制造汗腺 功能、精确的神经支配和神经元控制是不可或缺的。神经元信号会引起出汗；但是 此外，根据我们实验室以前的工作，汗腺成熟是必需的。汗腺和神经元依赖于 神经输入如何影响汗液，我们知之甚少。 腺体发育，尤其是汗腺干细胞。我们假设神经元神经支配是 对于汗腺干细胞在发育过程中的维持至关重要。用小鼠汗腺作为 作为一个模型，我们将研究汗腺干细胞在发育过程中的分子变化 缺乏神经支配，并进一步确定汗腺干细胞内介导 神经递质在干细胞维持中的作用。这项建议旨在：1)调查 汗腺发育过程中的神经元输入II)了解汗腺中神经递质的作用 发展III)研究钙是否参与汗腺干细胞的神经元控制。这些 研究将更深入地了解神经是如何调节汗液的发育和维持的。 腺体。此外，这一提议将为汗腺和神经元如何 发展成为对再生疗法有用的功能单元。

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.