Atlas of autonomic and neuromodulatory lineages in the developing lower urinary tract

项目总结 下尿路(LUT)的正常功能需要神经元活动的协调才能允许膀胱 充填以储存尿液，随后进行膀胱收缩，以在适当的时间完成排空 和地点。尽管人们对LUT的神经解剖学和成熟的电路有很多了解， 对DISTINCT的分子组成、发育和出生后成熟的了解相对较少 调节膀胱收缩能力的神经元亚型。目前，我们缺乏由以下基因表达的受体的目录 不同类型的盆神经节神经元可用于研究这些关键神经元是如何到达的 它们的靶点在不同的LUT器官或在手术损伤的情况下直接再生努力。更少的是 已知尿路中化学感觉刷状细胞和动脉瘤旁的分子组成 定位于调节LUT的收缩能力。这些细胞含有高水平的神经递质，因此可以 发挥神经调节剂的作用，刺激膀胱收缩，以应对感染或机械拉伸。 关于盆神经节运动神经元与这些神经调节细胞联系的认识 将能够对膀胱对感染的敏感性和收缩能力进行详细的机制研究， 炎症或尿液成分。GUDMAP Atlas项目的总体目标是在 知识，以便能够继续进行未来的机械学研究。提出了四个具体目标：(1) 编制发育过程中盆神经节神经元在单细胞分辨率下表达的基因图谱 和出生后成熟；(2)绘制了尿路神经调节细胞的首次出现和分布图 在小鼠发育过程中；(3)确定尿路神经调节细胞亚群的遗传标记 通过rna-seq；(4)生成详细的神经末梢的空间和时间图 神经调节细胞和感觉或自主盆神经节神经元。这些研究将产生新的 GUDMAP数据库目前缺乏的信息。我们的结果将用图表加以总结。 GUDMAP网站上的教程地图和确定的基因组将加快 人体组织。因此，研究界将能够研究特定细胞的功能 使用细胞类型和基因特异性方法的类型和检验假说。

PROJECT SUMMARY Normal function of the lower urinary tract (LUT) requires coordination of neuronal activities to allow bladder filling for urine storage later followed by bladder contraction to accomplish emptying at an appropriate time and place. Despite the fact that much is known about the neuroanatomy and mature circuitry of the LUT, relatively little is known about the molecular composition, development and postnatal maturation of distinct neuron subtypes that regulate bladder contractility. At present we lack a catalog of receptors expressed by different types of pelvic ganglia neurons that could be used to investigate how these critical neurons reach their targets in different LUT organs or direct regenerative efforts in cases of surgical damage. Even less is known about the molecular makeup of chemosensory brush cells and paraneurons in the urethra that are positioned to modulate LUT contractility. These cells contain high levels of neurotransmitters and thus can act as neuromodulators that stimulate bladder contraction in response to infection or mechanical stretch. Knowledge of the connections between motor neurons in pelvic ganglia and these neuromodulatory cells would enable detailed mechanistic studies of bladder sensitization and contractility in response to infection, inflammation or urine composition. The overall goal of this GUDMAP Atlas project is to fill these gaps in knowledge so that future mechanistic studies can be pursued. Four Specific Aims are proposed: (1) compile an atlas of genes expressed by pelvic ganglia neurons at single cell resolution during development and postnatal maturation; (2) map the first appearance and distribution of urethral neuromodulatory cells during development in the mouse; (3) identify genetic markers for subsets of urethral neuromodulatory cells by RNA-seq ; (4) generate a detailed spatial and temporal map of nerve terminals between neuromodulatory cells and sensory or autonomic pelvic ganglia neurons. These studies will generate novel information that is current lacking from the GUDMAP database. Our results will be summarized in diagrams and tutorial maps on the GUDMAP site and the gene sets identified will expedite comparative studies in human tissues. As a result the research community will be able to investigate the functions of specific cell types and test hypotheses using cell type and gene specific approaches.