Role of tissue mechanics in embryonic self-organization and cell fate plasticity
How molecular and mechanical cues interplay to coordinate the morphogenesis and patterning of embryonic structures is an open question in developmental biology. The early avian embryo is an ideal model for the study of such interplay as it exhibits highly regulative development, is greatly amenable to live imaging approaches and can be readily mechanically challenged. Whereas avian embryos have long been known to remarkably adapt and readjust cell fate upon surgical perturbations, such regulative potential has been investigated solely from a molecular standpoint, leaving the role for mechanical forces unexplored. This proposal builds on our recent results and methods characterizing the mechanical control of gastrulation to investigate the role of mechanical forces in embryonic regulation and in cell fate plasticity. Specifically, we propose 1) to develop innovative tools allowing to perturb the mechanical state of early embryos in order characterize the role of forces during development; 2) to test whether a mechanical self-organizing system underlies the remarkable regulative potential avian embryos; 3) to investigate the role of mechanical forces in mesoderm, embryonic and extra-embryonic regional fate allocation. To this end, we will use an interdisciplinary approach combining novel transgenic quail lines, live imaging, and pharmacological/molecular/optogenetic/mechanical perturbations along with theoretical frameworks and modeling approaches. These studies will decipher the interplay between cellular, molecular and mechanical cues that ensures the robust, yet plastic allocation of cell fate in amniote embryos (i.e. reptiles, birds and mammals, including humans).