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 neurotransmitters 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 fundamental principle of how two tissues (e.g., nerves and lungs) interact to build alveoli at the organismal level.

肺泡的形成增加了气体交换的表面积。对肺泡发生的分子理解仍然不完整。在这里，我们证明自主神经和肺泡肌成纤维细胞在小鼠中形成一个功能单位。肌成纤维细胞分泌神经营养因子以促进神经突延伸/存活，而从自主神经末梢释放的神经递质对于肌成纤维细胞增殖和迁移是必需的，这是肺泡发生的关键步骤。这在自主神经支配和肺泡形成之间建立了功能联系。我们还发现平面细胞极性 (PCP) 信号传导采用Wnt - Fz/Ror - Vangl级联调节细胞骨架和神经递质从自主神经末梢的运输/释放。这代表了 PCP 信号传导在赋予细胞特性方面的一个新方面。总之，这些研究提供了关于自主活动如何控制肺泡形成的分子见解。我们的工作还说明了两个组织（例如神经和肺）如何相互作用以在有机体水平上形成肺泡的基本原理。