Figure 3.

Alveolar stage. During alveolarization, alveolar area significantly increases by secondary septation, in which secondary septa subdivide the terminal sac. Elastic fibers and myofibroblasts exist at the tip of growing secondary septa. Outer layer of the capillary folds up to drive extension of the septa, in which new double-layered capillary exists (middle). At the later stage of alveolarization, these double layers of the capillaries in the secondary septa remodel to form a single layer of the capillary to facilitate septal thinning for efficient gas exchange (right). Alveolar capillary ECs produce retinoic acid (RA) and stimulate synthesis of elastin in myofibroblasts, which in turn stimulate capillary morphogenesis. Dynamic changes in the mechanical environment stimulate mechanosenstivie YAP1/TAZ signaling in pericytes to release Ang1 and HGF that act on ECs and AT2 cells and stimulate septation.