TRANSCRIPTIONAL TIMERS REGULATING MITOSIS IN EARLY DROSOPHILA EMBRYOS

Abstract

The development of an embryo requires a precise spatiotemporal regulation of cellular processes. We use transcriptional regulation of cdc25string and mitotic domains during Drosophila gastrulation as a model to demonstrate how a precise temporal pattern is established. Using a genetic screen, we demonstrate that the same spatial regulators of cdc25string transcription encode its temporal activation and identify buttonhead and empty spiracles as the major activators of cdc25string expression in mitotic domain 2. The effect of these activators is balanced through repression by hairy, sloppy paired 1 and huckebein. We show that a 500 bp enhancer element serves as an integrator to set the temporal pattern in mitotic domain 2 by measuring the levels of two activators buttonhead and empty-spiracles. Ectopic expression of these activators can override the intrinsic temporal pattern through the same enhancer element. Within the mitotic domain, temporal precision of mitosis is robust and is unaffected by changing dosage of rate-limiting transcriptional factors. Precision can however be disrupted by altering the levels of the two activators or two repressors. We propose that the additive and balanced action of activators and repressors is a general strategy for precise temporal regulation of cellular transitions during development.