Development of the respiratory system
Lung development requires the coordinated growth and morphogenesis of multiple cell populations: anterior foregut endoderm, splanchnic mesoderm, mesothelium, vasculature, lymphatics, immune cells and nerves. Together they give rise to the respiratory system which in the mouse consists of a trachea, two main bronchi and four right and one left lung lobes. Each lobe contains a branched, tree-like system of conducting airways ending in millions of highly vascularized alveoli specialized for gas exchange. Development begins with the formation of the trachea and two primary lung buds on the ventral anterior foregut; the buds then undergo extensive branching morphogenesis driven by reciprocal signaling interactions between the endoderm and mesoderm. Lineage tracing shows that distal tip cells are initially multipotent, giving rise to descendants in both intralobar airways and alveoli. Subsequently, the fate of tip cells becomes more restricted, and through further morphogenesis they generate only alveolar cells. Single cell transcriptomics and other studies have identified multiple distinct mesodermal populations. These contribute to airway and vascular smooth muscle, pericytes, and different fibroblast cell types, while the pulmonary blood system arises from an endothelial plexus present around the earliest lung buds. Alveolar development is a complex morphogenetic process that begins before birth and continues postnatally with the formation of secondary septa that greatly increase alveolar surface area for gas exchange. Conserved developmental mechanisms make the mouse a model for understanding human lung disorders but there are important species differences in cellular composition and organization to consider.
