Not all those who wander are lost: Specification of lung innervating sensory neurons

项目总结 多条证据表明外周神经系统在控制脑血管疾病中的重要性 器官功能。对于肺来说，神经支配在呼吸、肺血压和 感知气溶胶输入并对其做出反应的能力，例如过敏原。肺的感觉神经支配起源于 来自迷走神经节的神经元，轴突投射沿迷走神经(在拉丁语中意为“游荡”) 很有胆量。迷走神经投射到多个器官，包括气管、肺、心脏和肠道。多数 对迷走感觉神经元的研究主要集中在成年动物身上，而对迷走感觉神经元的了解还很少。 靶器官神经支配的发育。 迷走感觉神经元有不同的胚胎起源；颈静脉神经元起源于神经脊。 而结节神经元来源于鳃上胎盘。因为流浪汉的目标很多 神经节，神经元被指定为允许迷走神经感觉神经元的不同功能。越来越多的证据 显示迷走神经感觉神经元有多种亚型。例如，细胞内存在异质性 大小、神经传导速度、胚胎起源和基因表达。感觉神经元的多样性如何 是在发展过程中建立起来的，目前还不清楚。细胞是在靶器官之前还是之后指定的 神经支配是一个关键问题。 有一种观点认为，发育线索可能会使神经支配模式发生偏差，这一观点来自以下发现 支配肺的感觉神经元主要来自结节，而气管则主要由 颈静脉感觉神经元。我的目标是检验这一假设，即“不是所有游荡的人都迷路了”，并确定 迷走感觉神经元是在向目标器官发送投射之前指定的。要做到这一点，我将首先 确定迷走神经节投射到达靶器官(如气管和肺)的时间，以及 它们遵循血管或现有运动神经的提示(目标1)。我会确定是否存在异质性 肺神经支配前迷走感觉神经元之间的关系 靶器官支配前后的胚胎迷走神经节(目标2)。具体地说，我将确定 Trk受体在肺损伤前后颈静脉和结节感觉神经元中的表达 神经支配，并确定迷走神经感觉神经元的特性是否取决于神经营养配体的表达 器官神经支配之前或之后(目标2)。该项目将研究气管/肺的共同发育。 以及它们的神经，揭示了神经如何控制器官的基础知识 功能已建立。

PROJECT SUMMARY Multiple lines of evidence demonstrate the importance of the peripheral nervous system in the control of organ function. For the lung, neural innervation plays a key role in breathing, pulmonary blood pressure, and the ability to sense and respond to aerosol inputs such as allergen. Sensory innervation of the lung originates from neurons in the vagal ganglia with axonal projections along the vagus (which means “wandering” in Latin) nerve. The vagus nerve projects to multiple organs, including the trachea, lung, heart and intestine. Most studies on vagal sensory neurons have focused on adult animals, and little has been done to understand the development of target organ innervation. Vagal sensory neurons have distinct embryonic origins; jugular neurons are derived from neural crest while nodose neurons are derived from epibranchial placode. Because of the many targets of the vagal ganglia, neurons are specified to allow for the diverse functions of vagal sensory neurons. Increasing evidence shows that there are multiple subtypes of vagal sensory neurons. For example, there is heterogeneity in cell sizes, nerve conducting speed, embryonic origin, and gene expression. How the diversity of sensory neurons is established during development is not understood. Whether cells are specified before or after target organ innervation is a key question. A suggestion that developmental cues may bias the pattern of innervation comes from findings that the majority of lung innervating sensory neurons are from the nodose, while the trachea is mainly innervated by jugular sensory neurons. I aim to test the hypothesis that “not all those who wander are lost”, and determine if vagal sensory neurons are specified prior to sending projections to target organs. To accomplish this, I will first characterize when vagal ganglia projections reach target organs such as the trachea and lung, and whether they follow cues from blood vessels or existing motor nerves (Aim 1). I will determine if heterogeneity exists among vagal sensory neurons prior to lung innervation, based on an analysis of single-cell transcriptome of embryonic vagal ganglia before and after target organ innervation (Aim 2). Specifically, I will determine the expression patterns of Trk receptors within jugular and nodose sensory neurons prior to and after lung innervation, and determine if vagal sensory neuron specification depends on neurotrophic ligand expression before or after organ innervation (Aim 2). This project will investigate the co-development of the trachea/lung and their innervating nerves, and uncover the foundational knowledge of how the neural control of organ function is established.