Autonomic innervation regulates alveolar formation in development

项目摘要/摘要 这一建议发现了自主神经系统在控制肺泡形成中的一个新角色 肺部发育。这一发现开辟了一个新的调查领域，将增加我们的机械性 理解肺泡是如何形成的。来自拟议研究的知识具有重要的意义 用于治疗因肺泡未成熟或丧失而引起的人类肺部疾病。在这个提案中，我们将测试一个模型 其中自主神经支配和活动控制肺泡的形成。在这个过程中，平面细胞的极性 PCP信号调节神经递质的运输和释放。自主神经分泌的神经递质 神经控制肌成纤维细胞的增殖和迁移，这是肺泡形成的关键步骤。我们的具体目标 (1)检验肺自主神经支配在肺泡形成中起关键作用的假设； (2)检验平面细胞极性(PCP)信号控制神经递质转运的假设 在肺的自主神经末梢释放；以及(3)检验自主神经的假设 肌成纤维细胞的神经支配对其在肺泡形成过程中的功能至关重要。总而言之，这是 应用将揭示一种通过自主神经支配控制肺泡形成的新机制。它 也有可能提供新的策略，通过促进肺泡再生来刺激肺泡再生 神经再支配。

Project Summary/Abstract This proposal discovers a novel role of the autonomic nervous system in controlling alveolar formation during lung development. This finding has opened up a new area of investigation that will increase our mechanistic understanding of how alveoli are generated. Knowledge from the proposed study has important implications for treating human lung diseases caused by alveolar immaturity or loss. In this proposal, we will test a model in which autonomic innervation and activity control alveolar formation. In this process, planar cell polarity (PCP) signaling regulates neurotransmitter trafficking and release. Neurotransmitters secreted by autonomic nerves control myofibroblast proliferation and migration, a key step in alveolar formation. Our specific aims are: (1) To test the hypothesis that autonomic innervation of the lung plays a critical role in alveolar formation; (2) To test the hypothesis that planar cell polarity (PCP) signaling controls neurotransmitter trafficking and release at the autonomic nerve terminals in the lung; and (3) To test the hypothesis that autonomic innervation of myofibroblasts is critical for their function during alveologenesis. Taken together, this application will uncover a novel mechanism of controlling alveolar formation through autonomic innervation. It also has the potential to provide new strategies to stimulate alveolar regeneration by promoting lung reinnervation.