Role of Geometric Cues During Airway Smooth Muscle Patterning in the Developing Mouse Lung

Abstract

Branching morphogenesis is a process observed during the development of many tree-like organs including the lungs, mammary and salivary glands, prostate, and kidneys. Although biochemical signaling pathways have been studied intensively, research on the role of physical cues in branching morphogenesis is still limited. In this study, we focus on embryonic mouse lung development and airway smooth muscle (ASM), whose function is not fully understood but is increasingly believed to play an important role. ASM has recently gained more attention in lung morphogenesis since disrupting its pattern around the airway epithelium led to impaired lung growth. The immunofluorescent stains and quantification results in this study show that the spatial pattern of ASM is stereotyped during the four stages of terminal bifurcation. In addition, we report that the lines of maximum curvature of three-dimensional (3D) reconstructed airway epithelium qualitatively correspond to spatial patterns of ASM around the epithelium of newly forming branches. This suggests that the characteristic ASM pattern may follow the geometry of the epithelial tubes. Increasing our understanding of lung branching morphogenesis will help tissue engineers create artificial lungs, which will hopefully become a therapeutic in the future for patients suffering from lung diseases.