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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：
10366808
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/10366808
关键词：
Actomyosin Address Adult Alveolar Alveolus Antibodies Area Autonomic nervous system Behavior Cell Communication Cell Line Cells Coculture Techniques Cytoskeleton Defect Development Distal Distributional Activity 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 Pathogenesis Play Process Role Saccule structure Signal Pathway Signal Transduction Tamoxifen Testing Tetanus Toxin Time Validation Work autonomic nerve calcium indicator density fetal 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.

项目总结/文摘