Autonomic innervation regulates alveolar formation in development

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.