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This chapter explores the development, structure, and function of the lower airways. Sections 1 and 2 describe the anatomy, morphology, and distribution of the pulmonary innervation in pre- and postnatal murine, porcine, and human lungs. Recent advances in techniques (e.g., confocal microscopy, optical projection tomography) are reviewed with respect to their use in mutant/transgenic models, which have increased our understanding of pulmonary innervation throughout the pseudoglandular, canalicular, and saccular stages of development. Significant advances in our understanding of the potential role of the neuroendocrine cell system, including neuroepithelial bodies, are examined with respect to the origins of chemo- and mechano-sensation in the lung and the impact on airway regulation. Section 3 addresses pre- and postnatal airway smooth muscle function, while Section 4 provides an overview of the role of muscarinic receptors in the lung. In summary, this chapter documents the innervation of the lung and airway smooth muscle throughout development.

Publisher Summary This chapter provides an overview of the development of airway innervation and reviews the functional behavior of the efferent nerves associated with the lower airways. The innervation and the airway smooth muscle (ASM) have recently been recognized as dominant, integral components of the developing lung. Both are present in the epithelial tubules of the embryonic lung bud shortly after it evaginates from the foregut. The ASM is functionally mature shortly after it is laid down, the growth and maturation of the innervation largely follows the morphological stages of lung development. In the human lung, the primary pattern of branching of the bronchial tree is established during the pseudoglandular stage, followed by elongation of airways with increased vascularization of the lung periphery in the canalicular stage. The development within the acinus (thinning of epithelial cells, expansion of the air space) occurs during the saccular stage. As lung development proceeds through gestation to postnatal life, comprehensive maps of the pathways of the nerves to their target tissues have provided unique views of the airway innervation. The neural tissue and ASM are an integral part of the lung from its inception, and persist in a dynamic state throughout gestation and into postnatal life.