Functional Genomic Analysis of the Periodic Transcriptome in the Developing Drosophila Wing

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 cellcycle-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 un-characterized 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.