Regulation of the cell cycle during early Xenopus development

Abstract

Maturation-promoting factor (MPF) is a partially purified M-phase-specific activity that induces meiosis in frog oocytes and is detectable in mitotic lysates from cells of wide phylogenetic origins. We show here that without protein synthesis, addition and removal of MPF can drive the mitotic cycle in frog eggs, including nuclear membrane breakdown and reformation, chromosome condensation and decondensation, and suppression and initiation of DNA replication on endogenous DNA and on injected plasmid templates. We have also studied M-phase arrest induced by injection of unfertilized egg cytoplasm and show that this arrest blocks an endogenous cytoplasmic cell-cycle oscillator and causes the stabilization of MPF activity. The oscillator can be restarted by injection of Ca++, which causes chromosome decondensation, reinitiation of DNA replication, and loss of MPF activity. We have looked in more detail at how DNA replication responds to the level of MPF and show that the effects are on the chromatin template and not the replication machinery. These results suggest that in Xenopus embryos cell-cycle events of the nucleus, including DNA replication and mitosis, are controlled by the level of MPF activity, which is driven by or may be part of an autonomous cell-cycle oscillator. The way in which a more complicated somatic cell cycle may arise from the simple embryonic cell cycle is discussed.