Spatiotemporal dynamics of primary and motile cilia throughout lung development

Cilia are specialized structures found on a variety of mammalian cells, with variable roles in the transduction of mechanical and biological signals (by primary cilia, PC), as well as the generation of fluid flow (by motile cilia). Their critical role in the establishment of a left-right axis in early development is well described, as is the innate immune function of multiciliated upper airway epithelium. By contrast, the dynamics of ciliary status during organogenesis and postnatal development is largely unknown. In this study, we define the progression of ciliary status within the endothelium, epithelium, and mesenchyme of the lung. Remarkably, we find that endothelial cells (ECs) lack PC at all stages of development, except in low numbers in the most proximal portions of the pulmonary arteries. In the lung epithelium, a proximodistal ciliary gradient is established over time, as the uniformly mono-ciliated epithelium transitions into proximal, multiciliated cells, and the distal alveolar epithelium loses its cilia. Mesenchymal cells, interestingly, are uniformly ciliated in early development, but with restriction to PDGFR+ fibroblasts in the adult alveoli. This dynamic process in multiple cellular populations both challenges prior assertions that PC are found on all cells, and highlights a need to understand their spatiotemporal functions. HighlightsO_LIPrimary cilia are found broadly throughout early embryonic tissues. C_LIO_LIPrimary cilia are observed in both epithelial and mesenchymal cells in the early lung. C_LIO_LIPulmonary endothelial cells largely do not possess primary cilia during embryonic development. C_LIO_LIDifferential multiciliation and loss of epithelial cilia in a proximal-distal axis. C_LIO_LIMaintenance of cilia in adult pulmonary PDGFR+ fibroblasts. C_LI