Momen-Roknabadi Amir, Di Talia Stefano, Wieschaus Eric
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Cell Rep. 2016 Sep 13;16(11):2793-2801. doi: 10.1016/j.celrep.2016.08.034.
The development of an embryo requires precise spatiotemporal regulation of cellular processes. During Drosophila gastrulation, a precise temporal pattern of cell division is encoded through transcriptional regulation of cdc25(string) in 25 distinct mitotic domains. Using a genetic screen, we demonstrate that the same transcription factors that regulate the spatial pattern of cdc25(string) transcription encode its temporal activation. We identify buttonhead and empty spiracles as the major activators of cdc25(string) expression in mitotic domain 2. The effect of these activators is balanced through repression by hairy, sloppy paired 1, and huckebein. Within the mitotic domain, temporal precision of mitosis is robust and unaffected by changing dosage of rate-limiting transcriptional factors. However, precision can 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.
胚胎的发育需要对细胞过程进行精确的时空调控。在果蝇原肠胚形成过程中，通过对25个不同有丝分裂区域中的cdc25（string）进行转录调控，编码了一种精确的细胞分裂时间模式。通过遗传筛选，我们证明调控cdc25（string）转录空间模式的相同转录因子编码其时间激活。我们确定纽扣头和空气门是有丝分裂区域2中cdc25（string）表达的主要激活因子。这些激活因子的作用通过毛状、草率配对1和哈克贝因的抑制作用来平衡。在有丝分裂区域内，有丝分裂的时间精度很强，不受限速转录因子剂量变化的影响。然而，通过改变两种激活因子或两种抑制因子的水平，精度可能会受到干扰。我们提出，激活因子和抑制因子的累加和平衡作用是发育过程中细胞转变精确时间调控的一般策略。
