Emerging mechanisms regulating mitotic synchrony during animal embryogenesis

The basic mechanisms controlling mitosis are highly conserved in animals regardless of cell types and developmental stages. However, an exceptional aspect of mitosis is seen during early animal embryogenesis in which a large fertilized egg is quickly divided into smaller blastomeres according to the reproducible spatiotemporal pattern that does not rely on the cell-cycle arrest or growth. This mitosis, referred to as cleavage, overlaps in the timeframe with the specification of cell fate. The precise spatiotemporal regulation of cleavages is therefore essential to the creation of the appropriate cell number and to the morphology of an embryo. To achieve the reproducibility of cleavage during embryogenesis, the relative timing of mitosis between cells, which we refer to as synchrony, must be properly regulated. Studies in model organisms have begun to reveal how the synchrony of mitosis is regulated by the developmental modulation of cell-cycle machineries. In this review, we focus on three such mechanisms: biochemical switches that achieve the synchrony of mitosis, the nucleo-cytoplasmic ratio that provokes the asynchrony of mitosis, and the transcriptional mechanisms coupled with cell fate control that reestablish the synchrony of mitosis in each fate-restricted compartment. Our review is an attempt to understand the temporal patterns of cleavages in animal embryos created by the combinations of these three mechanisms.