Our lab has pioneered the use of live-imaging approaches to study how the preimplantation embryo forms. Our findings have revealed heterogeneities in transcription factor dynamics in the early mouse embryo, which predict the specification of the first differentiated cell lineages (the ICM and trophectoderm). We have also discovered many new forms of cytoskeletal organization that regulate the establishment of cell polarity and tissue organization in the embryo, a new type of mitotic spindle that drives the first asymmetric cell divisions, and nuclear mechanosensing processes that enable cells to integrate mechanical forces with fate decisions in vivo.