How the lung folds itself: biophysical insights from evolution

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Evolution has generated an enormous diversity of biological form. Given this diversity, it is highly likely that every tissue structure that one can imagine has been built by the embryo of one species or another. We are interested in uncovering the physical (mechanical) mechanisms by which epithelial sheets fold themselves into branching tubes in the embryo, and using those mechanisms to engineer tissues in culture. Over the past half century, developmental biologists have identified several biochemical signaling pathways and genetic control mechanisms necessary for tissue morphogenesis. In parallel, biological systems must obey Newton’s laws of motion, and physical forces need to be generated in order to sculpt simple populations of cells into complex tissue forms. Inspired by the evolutionary diversity of embryonic forms, we have combined time‐lapse imaging analysis with computational modeling and engineered tissue models to identify the mechanical forces and downstream signaling pathways that are responsible for generating the diverse architectures of the lungs from birds, mammals, and reptiles. I will describe our recent insights into the different physical mechanisms used to fold the epithelium across these three classes of vertebrates, and possible explanations for the divergence of the avian lung.