Inhibiting cyclin:Cdk in the Drosophila early embryo uncouples the mid blastula transition from the nuclear to cytoplasmic ratio

Rapid and synchronous syncytial mitotic cycles without gap phases characterize the initial phase of Drosophila embryogenesis. Starting at cell cycle 10, incremental and progressive increases in S phase duration lengthen these cycles, and an early transcriptional cascade that guides later events begins. After mitosis 13, an abrupt lengthening of S-phase, a dramatic increase in zygotic transcription, the first dependency on zygotic transcription, and onset of morphogenesis at cell cycle 14 mark the Mid Blastula Transition (MBT). These events in Drosophila are emblematic of animal embryos in general, which initiate embryonic patterning at gastrulation only after amplifying the number of nuclei to accommodate the disproportionately large cytoplasm of the fertilized egg. The transition from nuclear amplification stage to morphogenesis is relatively abrupt and is accurately timed. Efforts to determine the means of embryonic timing have dismissed models involving counting of cell cycles or counting of total number of cells and have focused on findings that modification of the nuclear to cytoplasmic ratio (N/C) influences timing in embryos of diverse species. The current model holds that the embryo must attain a critical N/C before initiating the MBT. While the coordination of the numerous MBT events is potentially complex, it is usually held that transcriptional activation at a threshold N/C activates the various processes. While N/C clearly impacts the timing of early embryonic progression, it is less clear when or how it acts. We have tested a key component of the current model—that a threshold N/C is required at the time of the MBT. In our test, we arrest embryos in interphases before the MBT and assessed if these embryos advance to MBT stages. Here, we report that embryos arrested at an N/C lower than that found at the MBT are capable of undergoing MBT events including zygotic transcription, cellularization, and gastrulation. Furthermore, we report that Grapes/Chk1, a regulator required for onset of MBT events, is not necessary for embryos to advance to MBT stages when cyclin:Cdk activity is down-regulated