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Cell proliferation in animals must be precisely controlled, but the signaling mechanisms that regulate the cell cycle are not well characterized. A regulated terminal mitosis, called the second mitotic wave (SMW), occurs during Drosophila eye development, providing a model for the genetic analysis of proliferation control. We report a cell cycle checkpoint at the G1-S transition that initiates the SMW, and we demonstrate that Notch signaling is required for cells to overcome this checkpoint. Notch triggers the onset of proliferation by multiple pathways, including the activation of dE2F1, a member of the E2F transcription factor family. Delta to Notch signaling derepresses the inhibition of dE2F1 by RBF, and Delta expression depends on the secreted proteins Hedgehog and Dpp. Notch is also required for the expression of Cyclin A in the SMW.

Original publication




Journal article


Dev Cell

Publication Date





529 - 539


Animals, Cell Cycle, Cell Cycle Proteins, Cell Proliferation, Cyclin A, DNA-Binding Proteins, Drosophila Proteins, Drosophila melanogaster, E2F Transcription Factors, Embryonic Structures, Gene Expression Regulation, Hedgehog Proteins, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Morphogenesis, Photoreceptor Cells, Invertebrate, Receptors, Notch, Signal Transduction, Transcription Factors, Transcription, Genetic