Lung developmental biology: an important key to regeneration in apparently adult onset disease

Chronic lung disease is the 4 th most common cause of death in adults world wide and the disease burden is increasing, in contrast to cancer and heart disease that are coming under control. Therefore research devoted to finding innovative ways to prevent or treat chronic lung disease should be a major public health priority. The lung develops as an anterior endodermal derivative of the foregut, which undergoes stereotypic rounds of branching morphogenesis in response to complex mesenchymally derived inductive signals. Crosstalk between between the compartments of the lung including mesothelium, mesenchyme, endothelium and nerves need to be correctly coordinated in time and space for morphogenesis to occur in the proper sequence. The same principles apply during alveolarization and postnatal growth of the lung. Severe disruption of this complex program results in absence of the lung, or if somewhat milder, neonatal lethality. Milder yet disruptions interfere with completion of alveolarization, and as a consequence of this confer susceptibility to disease and environmental exposures such as cigarette smoke and particulates. Since lung function falls inexorably past middle age in humans, the original functional endowment determines the starting point for decline. Correct integration of lung progenitor cell function during development is therefore key to prevention of apparently adult onset lung disease, while exogenous stem/progenitor cells, by enhancing regeneration, may be able to stave off the decline or even correct lung function.