Transcriptional Timers Regulating Mitosis in Early Drosophila Embryos.
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.
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Amir
A
Momen-Roknabadi
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: stefano.ditalia@duke.edu.
Stefano
S
Di Talia
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: efw@princeton.edu.
Eric
E
Wieschaus
D000818:Animals; D020029:Base Pairing / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D008938:Mitosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D014157:Transcription Factors