Chapter 1 - Molecular Bases for Lung Development, Injury, and Repair

Abstract

The first breath taken by newborns after birth initiates the transition from fetal to neonatal life. Successful transition is dependent on the establishment of effective gas exchange in the lungs. This exchange takes place in the alveoli, the terminal units of the lung. The embryonic lung undergoes branching morphogenesis to form a vast network of branched airways and subsequent formation and multiplication of alveoli by septation during the late stage of fetal lung development. These developmental processes are regulated by diverse crosstalk between the airway epithelium and surrounding mesenchyme, which are highly coordinated by transcriptional factors, growth factors, and extracellular matrix. Bronchopulmonary dysplasia is a chronic lung disease of premature infants that results from a developmental arrest of the immature lung caused by injurious stimuli such as mechanical ventilation, oxygen exposure, and intrauterine or postnatal infections. This chapter provides a brief overview of normal lung developmental processes, the key signaling pathways and proposed models in regulating lung budding, branching morphogenesis, alveolarization and vascular development, and the mechanism by which injury from mechanical ventilation and oxygen exposure modulates some of these key pathways, thus affecting neonatal lung development in the context of prematurity.