ZYGOTIC TRANSCRIPTION IS REQUIRED TO BLOCK A MATERNAL PROGRAM OF APOPTOSIS IN XENOPUS EMBRYOS

At the midblastula transition during Xenopus development, the cell cyc le is remodeled, and zygotic transcription is initiated. Additionally, cyclin El is degraded at the midblastula transition independently of protein synthesis, the number of cell cycles, and the nuclear-to-cytop lasmic ratio. In the studies reported here, cell cycles were delayed b y transient inhibition of protein synthesis with cycloheximide (100 mu g/ml) prior to the midblastula transition. Even after reaccumulation of mitotic cyclins and resumption of cell divisions, cycloheximide-tre ated embryos did not resume DNA synthesis, failed to initiate transcri ption, and synchronously became apoptotic before the gastrula stage. T hese results were independent of the stage at which embryos were treat ed or the duration of treatment. Inhibition of zygotic transcription w ith alpha-amanitin also induced apoptosis. These data suggest that a d evelopmental checkpoint at the midblastula transition is maternally re gulated and can trigger apoptosis. Apoptosis induced by cycloheximide or cr-amanitin was blocked by injection of RNA encoding Xenopus Bcl-2, suggesting that this maternal program is normally blocked by expressi on of an apoptotic inhibitor. Embryos pulsed with lower doses of cyclo heximide (10 mu g/ml) delayed development prior to the midblastula tra nsition but resumed DNA synthesis, initiated transcription, and gastru lated normally. This indicates that the apoptotic response is initiate d only when delayed embryos are unable to support initiation of zygoti c transcription. (C) 1997 Academic Press.