At a certain point in the development of most animal embryos, the mid-blastula transition (MBT), cell cycle progression slows down, and developmental control switches from maternal factors to zygotic transcripts. How are these two concurrent events controlled? Here, Eric Wieschaus and colleagues report that in Drosophila, total DNA content regulates both cell cycle slowing (CCS) and the zygotic transcription of select genes,whereas most zygotic transcription begins after a set timespan (see p. 2101). CCS depends on the ratio of nuclear content to cytoplasmic volume (the N/C ratio); using chromosome rearrangements, the researchers now demonstrate that CCS is independent of any particular genome region and requires an N/C ratio above 70% of that in wild-type embryos. They also demonstrate that, whereas most zygotic transcription depends on a timing mechanism independent of the N/C ratio, a set of 88 genes is N/C ratio-regulated. Thus, the researchers propose two independent mechanisms exist that control the onset of zygotic transcription, one of which correlates with CCS.