BIO/BME Faculty Search Seminar; Dr. Rui Yan

Title: "Multiscale Biophysical Mechanisms of Foregut Morphogenesis"

Abstract: During embryonic development, cells and tissues are organized into functional organs through morphogenesis, a dynamic yet robust process despite continuous growth and remodeling. Understanding how morphogenesis works will deepen our knowledge of biological design principles and the developmental origins of human disease. Although genetic studies have identified many of the signaling pathways involved in organ formation, much less is known about the biophysical forces that shape internal organs, in part because they are difficult to visualize and manipulate in vivo. In this talk, I will describe the development of embryonic tissue explant models to uncover the biophysical mechanisms that drive foregut morphogenesis, which gives rise to the esophagus, trachea, and lungs. Combining quantitative live imaging with biomechanical and pharmacological perturbations, we found that mesenchymal cell migration generates compressive forces driving tracheal-esophageal separation, whereas epithelial growth generates expansive forces that contribute to left-right asymmetric lung development. At the molecular level, these forces are coordinated by reciprocal signaling between tissues, supporting a mechano-chemical feedback model for robust morphogenesis. Comparative studies in mouse and chicken embryos further reveal evolutionarily conserved and speciesspecific mechanisms underlying foregut morphogenesis. This work establishes a multiscale framework for understanding both the design principles of life and the biophysical origins of birth defects.