Figure 2.

Canalicular and saccular stage. (A) During canalicular stage, distal airway is further expanded and vascularized by capillaries. Distal multipotent epithelial progenitor cells differentiate into AT1 and AT2 at the alveolar wall. The source of VEGF is completely shifted from mesenchyme to epithelium, which facilitates closer interaction between epithelium and endothelium. This close interaction also contributes to differentiation of the epithelial progenitor cells into AT1 and AT2 cells. Endothelial and epithelial basement membrane (BM) fuse to form layered BM. BM-bound VEGF and other growth factors (GFs) modulate self-renewal and differentiation of AT2 cells. (B) During saccular stage, primitive alveoli are formed, in which alveolar epithelium and capillary endothelium form the interface for gas-exchange by sharing their basement membrane. This process includes further thinning of AT1 cells. Thick primary septa, which include double-layered capillaries, are formed between the walls of primitive alveoli. EC-derived angiocrine factors such as HGF and NO stimulate alveolar epithelial cell maturation and morphogenesis.