Morphogenesis is the process by which simple tissues fold into the complex shapes of mature organs, such as the branching airways of the lung. This tissue folding is caused by patterns of mechanical forces (pushing and pulling the tissue) that are induced by the expression of different genes throughout the tissue. The final shapes of the lungs of mammals, birds, and reptiles are vastly different, suggesting that the mechanical forces and genes expressed are different as well. This award supports fundamental research to define the gene expression changes and mechanical forces that fold the airways of the lungs in three different species (mouse, chicken, and alligator). Understanding what is unique and what is conserved between lungs of different species will provide insight into how different organs evolved over time. Additionally, being able to manipulate the expression of genes to control organ development is critical for tissue engineering applications for the biomedical and healthcare industries. Results from this research will therefore have economic and societal benefits for the United States. This research combines techniques and insights from several disciplines, including developmental biology, mechanobiology, and biomedical engineering. This interdisciplinary approach will help broaden the participation of underrepresented minority groups (at the undergraduate and high school levels) and enhance outreach interactions with the lay population.
Mammals, birds, and reptiles have evolved different anatomical strategies for the conduction and diffusion of air through the lungs, which must result from differences in airway morphogenesis in the embryo. The objective of this project is to define and quantify these evolutionary morphogenetic differences. The research team will use three-dimensional traction force microscopy, real time confocal imaging, and continuum mechanical modeling to quantify the forces exerted during morphogenesis of the distinct airway architectures of embryonic mice, chicks, and alligators. In parallel, high-throughput gene expression analysis will be conducted for each morphogenetic movement in each species. These analyses will reveal the distinct gene expression changes that control mechanical forces within the epithelium as it folds lateral branches (mammals and birds), bifurcating branches (mammals and reptiles), and anastomosing airways (birds and reptiles). This research adopts for the first time the principles of mechanobiology within the framework of evolutionary developmental biology to create a comprehensive physical description of tissue morphogenesis, and will uncover the basic mechanical differences underlying lung development in different species.
