COORDINATION · Coordination of mouse embryogenesis in space and time at implantation

Self-organisation is a defining feature of living systems and entails complex interplay between multiple parameters across various spatio-temporal scales. Using pre-implantation mouse embryos as a model system, our studies revealed a principle of regulative development, in which feedback between cell fate, polarity and mechanics ensures robust control of embryo size, shape and pattern. However, as embryos undergo implantation, this self-organisation mechanism has to be integrated in its spatio-temporal context. In this project, we aim to understand how developmental mechanisms are coordinated in space and time. The peri-implantation mouse embryo is an attractive system in which to study this coordination, as it begins to interact with uterine tissues, marks a key transition in morphogenesis, cell cycle and growth, and exhibits a remarkable capacity for size regulation. We recently developed an ex vivo 3D culture, engineered uterus and light-sheet microscopy to recapitulate morphogenesis and embryo-uterus interactions, and analyse changes in cell shape, fate, polarity and mechanics. Using these new methods, we aim to mechanistically understand the transformation from blastocyst to egg cylinder as embryonic-extraembryonic tissues interact. We will use embryo size control as a paradigm to study the coordination of developmental programmes in space and time. At the cellular level, we will identify what triggers the transition from cleavage to proliferative cell cycle – mammalian mid-blastula transition. At the embryonic level, we aim to understand how animal size is sensed and changes the temporal progression of development. Finally, we will investigate the role of embryo-uterus interactions in embryo morphogenesis and positioning within the uterus. The bottom-up engineering approaches will be complemented by top-down intravital microscopy to monitor embryogenesis in utero. Together, this project will bring mammalian developmental biology into a new stage.