A functional circuit formed by the autonomic nerves and myofibroblasts controls mammalian alveolar formation for gas exchange

Alveolar formation increases the surface area for gas exchange. A molecular understanding of alveologenesis remains incomplete. Here, we show that the autonomic nerve and alveolar myofibroblast form a functional unit in mice. Myofibroblasts secrete neurotrophins to promote neurite extension/survival, whereas neuro-transmitters released from autonomic terminals are necessary for myofibroblast proliferation and migration, a key step in alveologenesis. This establishes a functional link between autonomic innervation and alveolar formation. We also discover that planar cell polarity (PCP) signaling employs a Wnt-Fz/Ror-Vangl cascade to regulate the cytoskeleton and neurotransmitter trafficking/release from the terminals of autonomic nerves. This represents a new aspect of PCP signaling in conferring cellular properties. Together, these studies offer molecular insight into how autonomic activity controls alveolar formation. Our work also illustrates the funda-mental principle of how two tissues (e.g., nerves and lungs) interact to build alveoli at the organismal level.

Automated summary

The autonomic nerve and alveolar myofibroblast form a functional unit in mice, where myofibroblasts secrete neurotrophins to promote neurite extension/survival and neurotransmitters released from autonomic terminals are necessary for myofibroblast proliferation and migration. Planar cell polarity signaling regulates the cytoskeleton and neurotransmitter trafficking/release from autonomic nerves.