(138c) Mechanical Wrapping By Smooth Muscle Directs Epithelial Morphogenesis in the Lungs

All terrestrial vertebrates rely on lungs to extract oxygen from the air and expel carbon dioxide generated in body tissues, but the structure of these lungs is not the same across the animal kingdom. The mammalian lung consists of a complex, tree-like structure, wherein branched airways terminate in alveoli that exchange gases with the blood. In the avian lung, airways that begin terminally branched during development eventually come together and fuse, creating a closed circuit of airways that interweave with vasculature to exchange gases. The most basic lung structures are found in reptiles, some of which have lungs which are simple epithelial pouches with only rudimentary corrugations along the surface to increase surface area. Through understanding the physical mechanisms that build these different structures, and reverse-engineering them, we will unveil novel techniques for tissue engineering. We recently found that patterned differentiation of airway smooth muscle drives branching morphogenesis of the epithelium in the mouse lung, but to date this mechanism is unexplored in other systems. Here, we examined the possible role for airway smooth muscle in sculpting airway fusion in the bird and airway corrugation in the reptile. We found that prior to airway fusion in the domestic chicken, Gallus gallus, the airways initiate branches in the direction of their target, which contain the cells that will make the first contact. These new branches are similar in morphology to the branches observed in the early mouse lung, with a similar pattern of smooth muscle coverage, suggesting a role for smooth muscle in shaping the airways and facilitating fusion. We have also examined early development of the reptile lung using the brown anole, Anolis sagrei. We found that smooth muscle is present in a mesh-like pattern around the lung epithelium and regulated by the same molecular signaling pathways as in the murine lung. Epithelial corrugations form in the gaps between the smooth muscle mesh. Furthermore, altering the pattern of smooth muscle or inhibiting its ability to contract prevents epithelial morphogenesis. Despite the fact that the tissue forms in different patterns and at different times in development, these data suggest that smooth muscle can be used to shape epithelial tissues into a variety of final architectures. We aim to use these insights to manipulate smooth muscle differentiation in the developing lung in order to direct epithelial morphogenesis, ultimately gaining precise mechanical control over these developing tissues.