Chapter 1: Lung Pattern Formation and Development

The major function of the lung in different organisms is to perform an efficient exchange of gas with the atmosphere. The thickness of the surface of gas diffusion of the mature lung is 1 micron in humans. However, this produces a surface area of 70 square meters, which is equivalent in size to a modern tennis court or the wing surface of a small aircraft. The lung has a complex organization within the chest as a honeycomb-like structure that comprises a network of extensively branched ducts that function to conduct air to and from the alveolar gas exchange surface. This occurs in a configuration that remarkably increases the surface that facilitates gas exchange between blood and air, while enabling maximally efficient packing of this surface within the chest cavity. This complex structure of the lung is developed sequentially by early branching of the epithelial tube and later on by the process of the septation of terminal air sacs. In addition, the development of pulmonary vasculature that occurs in conjunction with epithelial branching morphogenesis acts to facilitate the transport of respiratory gases to and from the developing alveolar surface. In conjunction with these developmental processes, the development of airway smooth muscle (ASM) takes place during early lung morphogenesis, and its contraction may function to regulate the growth of the lung. Any perturbation of these tightly regulated developmental processes can lead to the formation of abnormal lung structure, gas exchange deficiency and/or respiratory failure. Such disruption of normal lung growth and development is clinically exemplified in many cases, such as premature human delivery, bronchopulmonary dysplasia, or congenital lung defects or disorders. This chapter will describe different phases of lung development, genetic control of the formation pattern of early lung anlagen, distal airway branching morphogenesis, and the alveolar septum formation and its regulatory factors and molecular mechanisms as well as the development of various lung-specific cell types.