Figure 2.

(A) During early human embryo development, the inner cell mass differentiates and becomes organized in the epiblast and hypoblast layers. Primitive streak formation leads to an ingression movement of epiblastic cells that elongate and detach from each other via a critical epithelial–mesenchymal transition [31]. This results in the formation of the three germ layers: ectoderm, mesoderm and endoderm. (B) On day 22, the foregut forms a ventral outgrowth leading to the formation of larynx and trachea in its proximal part, and lung buds in the distal part. Bifurcation and splitting of the lung buds give rise to the future right and left lungs. These structures grow ventrally to caudally through the surrounding mesenchyme. Mesenchymal progenitor cells secrete many factors, including fibroblast growth factor 10 (FGF10) that interacts with fibroblast growth factor receptor (FGFR) expressed by distal epithelial cells. Moreover, some cytokines, such as bone morphogenic protein 4 (BMP4), are secreted by both epithelial and mesenchymal cells.