MechanoFate · Morphogenesis meets Cell Fate: Dissecting how Mechanical Forces coordinate Development

During embryonic development, an unspecialized cell mass is transformed into complex tissues and organs through collective movements and cell interactions. The acquisition of such structural and functional diversity is powered by two main processes: morphogenesis, which sculpts cells into tissues and organs, and cell fate acquisition, which assigns specific identities to cells. Despite extensive research, the intricate coordination between these two processes remains elusive. Mechanical forces determine the shape and structure of tissues, and their impact on cell fate has been recently uncovered, emphasizing the significance of mechanics in regulating both morphogenesis and cell fate. However, understanding the relationship between these two processes is complex, as it requires the integration of cell shape, cell behavior, mechanics, and gene expression across the tissue over time. In this project, we will apply cutting-edge biophysical and data science methods to the mucociliary epithelium of Xenopus embryos to dissect the role of mechanics in both morphogenesis and cell fate acquisition in vivo. We will first determine how cells undergoing fate acquisition trigger local tissue rearrangements that lead to global morphogenetic movements. Next, we will investigate the impact of tissue mechanics on cell fate and transitions. Finally, we will combine cell behaviors, gene expression, and mechanics into a model to predict cell fate. By exploring the ways cells respond to and modify their mechanical surroundings and the circumstances in which external forces determine cell fate, we will uncover the basic principles of complex tissue formation. This research will give us a comprehensive understanding of how individual cells, as mechanical elements, interact to form a tissue structure that is more than just the sum of its parts. The findings will have a significant impact on other tissues, particularly the human airways, and advance our knowledge of embryonic development.