Protocol for lattice light-sheet time-lapse imaging of early post-implantation mouse embryos

Lattice light-sheet microscopy offers unprecedented spatial and temporal resolution for visualizing morphogenetic and physiological processes, while minimizing photodamage. Here, we present a detailed protocol for time-lapse imaging of post-implantation mouse embryos, using lattice light-sheet microscopy. We describe steps for embryo isolation, mounting and culture, setting up of imaging parameters, and pipelines for processing the data generated in preparation for downstream analyses. This approach is also suitable for stem cell-derived embryo models, organoids, and small organ explants. For complete details on the use and execution of this protocol, please refer to Thowfeequ et al.¹ and Stower et al.².