The eukaryotic cell cycle, driven by both transcriptional and posttranslational mechanisms, is the central molecular oscillator underlying tissue growth throughout animals. Although genome-wide studies have investigated cell-cycle-associated transcription in unicellular systems, global patterns of periodic transcription in multicellular tissues remain largely unexplored. Here we define the cell-cycle-associated transcriptome of the developing Drosophila wing epithelium and compare it with that of cultured Drosophila S2 cells, revealing a core set of periodic genes and a surprising degree of context specificity in periodic transcription. We further employ RNAi-mediated phenotypic profiling to define functional requirements for more than 300 periodic genes, with a focus on those required for cell proliferation in vivo. Finally, we investigate uncharacterized genes required for interkinetic nuclear migration. Combined, these findings provide a global perspective on cell-cycle control in vivo, and they highlight a critical need to understand the context-specific regulation of cell proliferation.
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