Epithelial-mesenchymal-endothelial-nerve-matrix crosstalk in early mouse lung . This concept figure diagrams many of the known interactions between these compartments in lung morphogenesis. In the proximal lung, Sox9-positive mesenchymal progenitors play a key role in inducing tracheal cartilage, which in turn plays an inductive role on tracheal epithelial progenitors. In the first generation of airways, FGF10 signaling from the mesenchyme exerts an inductive and chemoattractive effect on the lung epithelium , which are both required for the subsequent induction of the distal epithelial progenitors as well as organization of all the distal lung structures. In the peripheral epithelium, FGF10 is still an important inductive signal for peripheral progenitors as well as for branching. FGF10 progenitors in the peripheral mesenchyme also act as progenitors for distal airway smooth muscle under the influence of Shh and BMP4 signaling. Wnt signaling from distal epithelium induces fibronectin to be laid down in potential distal clefts and this is essential for cleft formation. The early pulmonary arteries connect with early distal capillaries that form from hemangioblasts under the control of VEGF secreted by the epithelium. The formation of capillary plexi is likewise essential for the sprouting of side branches from condensation so Sox9-positive epithelial progenitor cells . Sympathetic nerve fibers arise from ganglia in the mediastinum, cross the proximal airway and early pulmonary arteries in a stereotypic manner and then follow the superior surface of the airway all the way to the periphery of the lung. Both nerve twigs and single capillary branches can be found between each lung epithelial cleft. FGF9 is expressed by the primitive mesothelium and induces FGF10 within the subjacent distal mesenchyme. Calcium ion waves arise from pacemakers in the mediastinum and proximal bronchi and pass down the bronchi toward the periphery, orchestrating distal-wards peristaltic waves that increase pressure within the peripheral airway tips. Peripheral tip progenitors can be identified by the co-expression of large number of characteristic transcriptional factors, growth factor receptors, and downstream signaling molecules that control their behavior