Speaker
Description
Gastrulation represents a critical symmetry-breaking event in embryo development, culminating in the specification of all major cell types and the establishment of the body axes. Taking advantage of a two-dimensional (2D) in vitro system derived from human pluripotent stem cells, termed gastruloid discs, we are investigating the molecular and biophysical mechanisms driving human gastrulation. By establishing a high-throughput morphometric pipeline, we found that extraembryonic amnion cells adopt a squamous organization, while the differentiated epiblast remains largely columnar – recapitulating the shape signatures of the 3D human embryo. Through direct force measurements, biophysical modelling, and targeted perturbations, we found that the squamous transition in the amnion is driven by active wetting, i.e. a transition from tension to adhesion dominated cellular states. This is molecularly achieved via the rewiring of cytoskeletal composition in the amnion, from actomyosin to keratin-based networks. We are now investigating whether these shape changes are required for amnion specification and whether they are mechanically transmitted to the embryonic compartment. Overall, this multiscale approach is providing an entry point to understand the regulation and functional role of mechanical forces in human gastrulation.