Notch activity opposes ras-induced differentiation during the second mitotic wave of the developing Drosophila eye

Background: EGF receptor acts through Ras and the MAPK cascade to trigger differentiation and maintain survival of most of cell types in the Drosophila retina. Cell types are specified sequentially by separate episodes of EGFR activity. All the cell types differentiate in G1 phase of the cell cycle. Before differentiating, many cells pass through the cell cycle in the "Second Mitotic Wave" in response to Notch activity, but no cell fates are specified during the Second Mitotic Wave. It is not known how fate specification is limited to G1-arrested cells. Results: Competence to differentiate in response to activated RasV12 was diminished during the Second Mitotic Wave accounting for the failure to recruit cell fates from cycling cells. Competence was not restored by blocking cell cycle progression, but was restored by reduced Notch activity. Conclusion: Competence to differentiate does not depend on cell cycle progression per se, but on the same receptor activity that also induces cell cycle entry. Dual effects of Notch on the cell cycle and on differentiation help ensure that only G1 phase cells undergo fate specification.