Timing of transcription and protein synthesis underlying morphogenesis in preimplantation mouse embryos

During preimplantation development of the mouse, embryos pass through a series of morphogenetic events: compaction, fluid accumulation to form the blastocoele (cavitation), and escape from the zona pellucida (hatching). We have used the inhibitors alpha-amanitin and cycloheximide to investigate the timing of transcriptional and translational events underlying these morphogenetic stages. Groups of embryos were transferred from a common pool into medium containing one or the other inhibitor at regular time intervals, and then were scored over the ensuing 24 or more hours for their ability to reach a particular morphogenetic end point. By comparing the time when the control population reached an end point with the time at which embryos had to be transferred into the inhibitor in order to prevent them from reaching that end point, we could determine when in advance of each event the necessary transcription or protein synthesis has been completed. Our results suggest that compaction (as well as cleavage to the eight-cell stage) is an embryonically, rather than maternally, programmed event, although the necessary transcription is completed well in advance, at least by the early four-cell stage. The transcriptional and translational events underlying fluid accumulation, on the other hand, appear to be completed within a few hours of the start of this process. For hatching, there is once again a long delay between the apparent time of completion of the necessary transcriptional events and the process itself, with protein synthesis being completed just a few hours in advance. Our results raise the possibility that post-transcriptional regulatory mechanisms play an important role in the timing of morphogenetic events in early mouse embryos.