PT  - JOURNAL ARTICLE
AU  - Isaac Strong
AU  - Kai Yuan
AU  - Patrick H. O’Farrell
TI  - Interphase-arrested <em>Drosophila</em> embryos initiate Mid-Blastula Transition at a low nuclear-cytoplasmic ratio
AID  - 10.1101/143719
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 143719
4099  - http://biorxiv.org/content/early/2017/06/01/143719.short
4100  - http://biorxiv.org/content/early/2017/06/01/143719.full
AB  - Externally deposited eggs begin development with an immense cytoplasm and a single overwhelmed nucleus. Rapid mitotic cycles restore normality as the ratio of nuclei to cytoplasm (N/C) increases. At the 14th cell cycle in Drosophila embryos, the cell cycle slows, transcription increases, and morphogenesis begins at the Mid-Blastula Transition (MBT). To explore the role of N/C in MBT timing, we blocked N/C-increase by downregulating cyclin/Cdk1 to arrest early cell cycles. Embryos arrested in cell cycle 12 cellularized, initiated gastrulation movements and activated transcription of genes previously described as N/C dependent. Thus, occurrence of these events is not directly coupled to N/C-increase. However, N/C might act indirectly. Increasing N/C promotes cyclin/Cdk1 downregulation which otherwise inhibits many MBT events. By experimentally inducing downregulation of cyclin/Cdk1, we bypassed this input of N/C-increase. We describe a regulatory cascade wherein the increasing N/C downregulates cyclin/Cdk1 to promote increasing transcription and the MBT.Impact statement By showing that cell-cycle arrest allows early Drosophila embryos to progress to later stages, this work eliminates numerous models for embryonic timing and shows the dominating influence of cell-cycle slowing.