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Autonomic innervation regulates alveolar formation in development

自主神经支配调节发育过程中的肺泡形成

基本信息

批准号：
10592271
负责人：
PAO-TIEN CHUANG
金额：
$ 57.85万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-15 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10592271
关键词：
Ablation Actomyosin Adult Alveolar Alveolus Antibodies Area Autonomic nervous system Behavior Cell Communication Cell Line Cells Coculture Techniques Cytoskeleton Defect Development Distal Enzymes Excision Fiber Human Immunofluorescence Immunologic Investigation Knowledge Label Ligands Lung Lung diseases Mediating Methodology Modeling Molecular Monitor Mus Myofibroblast Natural regeneration Neonatal Nerve Nerve Block Nerve Fibers Nerve Growth Factor Receptors Neural Crest Neural Crest Cell Neuromuscular Junction Neurons Neurotransmitter Receptor Neurotransmitters Output PC12 Cells Pathogenesis Play Process Proliferating Role Saccule structure Signal Pathway Signal Transduction Tamoxifen Testing Tetanus Toxin Time Work autonomic nerve calcium indicator density fetal inducible Cre lung development migration nerve supply neurotransmitter release neurotransmitter transport neurotrophic factor novel novel therapeutics planar cell polarity progenitor receptor reinnervation single-cell RNA sequencing trafficking transcriptome sequencing

项目摘要

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.

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。