High resolution mapping of lower urinary tract innervation during development

描述（由申请人提供）：成熟下尿路（LUT）的主要行为-储存和排泄取决于功能性神经系统。这些回路在产前时期的发展知之甚少。 出生后，有一个戏剧性的转变，从不成熟的情况下，排尿是“自动的”，即，不受大脑驱动的过程控制，到健康的成熟系统，其中填充触发有意识的排尿需求，但排尿是在适当的时间和地点自愿决定的。在青春期前后，膀胱、肠道和性活动的协调发生了进一步的变化。许多事件发生在神经系统在这些时期，虽然细胞位点和分子机制尚未确定。该分子解剖学GUDMAP Atlas项目的目标是绘制（i）产前和产后期间与小鼠下尿路形成的轴突连接的详细时间和空间分布图，以及（ii）可能启动和维持这些连接的因子/受体的表达。本项目将采用神经解剖学的方法，包括神经束追踪、免疫组织化学和原位杂交，以实现以下三个目标：（1）绘制小鼠发育和出生后成熟过程中LUT内感觉和运动轴突关键功能和化学类别的终末区域;（2）确定这一时期支配小鼠下丘脑的感觉神经元和自主神经元的结构和化学“指纹”;（3）绘制决定神经和小鼠LUT之间连接的神经营养和引导因子的细胞来源。构建这一知识基础对于理解这些连接如何形成（或未能形成）以及在健康，疾病或损伤状态下维持或调节它们的机制至关重要。建立发育和成熟膀胱神经元的结构和化学指纹图谱也将使研究人员能够解释GUDMAP数据库中的许多当前表达模式。更广泛地说，这些结果将促进对这些发育和成熟回路的理解，并为分析发育和成人泌尿生殖系统的可塑性和损伤反应提供坚实的基础。

DESCRIPTION (provided by applicant): The primary behaviors of the mature lower urinary tract (LUT) - storage and voiding depend on a functional nervous system. Development of these circuits in the prenatal period is poorly understood. Postnatal, there is a dramatic transition frm the immature situation where voiding is "automatic", i.e., not controlled by brain-driven processes, to the healthy mature system where filling triggers a conscious need to void, but micturition is determined voluntarily at an appropriate time and place. Around puberty, further changes occur to coordinate bladder, bowel and sexual activity. Many events occur in the nervous system over these periods, although the cellular loci and molecular mechanisms have not been defined. The goals of this molecular anatomy GUDMAP Atlas Project are to map (i) the detailed temporal and spatial profiles of axon connections that form with the mouse lower urinary tract during pre- and postnatal periods, and (ii) the expression of factors/receptors that may initiate and sustain these connections. The project will use robust neuroanatomical methods including tract tracing, immunohistochemistry and in situ hybridization to address three aims: (1) To map the terminal fields of key functional and chemical classes of sensory and motor axons within the mouse LUT during development and postnatal maturation; (2) To define the structural and chemical "fingerprint" of sensory and autonomic neurons innervating the mouse LUT during this period; (3) To map the cellular source of neurotrophic and guidance factors that determine connectivity between nerves and the mouse LUT. Constructing this knowledge base is essential to understand how these connections form (or fail to form) and the mechanisms that may sustain or modulate them in health, disease or injury states. Establishing a structural and chemical fingerprint of developing and mature bladder neurons will also allow researchers to interpret many of the current expression patterns in the GUDMAP database. More broadly, the outcomes will promote understanding of these developing and maturing circuits and provide a strong foundation to analyze plasticity and injury responses in the developing and adult urogenital system.