The midblastula transition

Once an egg is fertilized, intracellular Ca2+ is elevated, cyclin B degradation is stimulated, and CSF activity declines in concert with loss of MAPK and Rsk activity. The first 12 cleavage cycles occur with a cycle time of 26 min and display only M and S phase, except for the first cycle which is longer and has a detectable G2 phase (Fig. 1). Despite these short cycles, the enzymes that control Cdc2 Tyr15 phosphorylation, Wee1 and Cdc25A, are rapidly synthesized after fertilization and new cyclin B/Cdc2 complexes appear to undergo a rapid cycle of Tyr15 phosphorylation/dephosphorylation in every cell cycle. Since no G2 phase is evident in these cell cycles, the function of transient Tyr15 phosphorylation is not clear at this time. The prevailing view is that cell cycle checkpoints do not occur in the first 12 cycles because cleavage is unaffected by inhibition of DNA or RNA synthesis or microtubule depolymerization agents. However, at the MBT, cleavage is blocked by inhibition of DNA synthesis and if DNA is damaged or transcriptionally blocked, a maternally programmed apoptosis response is initiated (Anderson et al 1997). The events of the MBT fall into two classes: those that occur at a fixed time after fertilization and those that require a threshold nuclear:cytoplasmic ratio. Examples of the former include the degradation of maternal cyclin E, and of the latter cell cycle arrest by aphidicolin and zygotic transcription (Hartley et al 1997, Newport & Kirschner 1982). The developmental timing mechanism that controls cyclin E degradation has not been elucidated. In principle, it might have similarities to other fixed timing events in development identified in other organisms (Burton et al 1999). Although the timing of the MBT is independent of DNA, RNA and protein synthesis, the timing of cyclin E degradation and later MBT events is delayed by the Cdk inhibitor p27xic1, which inhibits cyclin E/Cdk2 (Hartley et al 1997). Centrosome duplication, which requires cyclin E, is also inhibited by Xic1 (Hinchcliffe et al 1999), suggesting the possibility the timing mechanism reflects some aspect of centrosome biology.

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