Abstract
BackgroundEGF 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.ResultsCompetence 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.ConclusionCompetence 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.
Highlights
EGF receptor acts through Ras and the MAPK cascade to trigger differentiation and maintain survival of most of cell types in the Drosophila retina
Based on recent findings that Notch signaling is essential for S-phase entry in the SMW[20,21], we propose that, in normal development, G1 phase cells differentiate because the Notch activity that promotes cell cycle entry interferes with differentiation
Reduced competence to differentiate during the Second Mitotic Wave The GMR-GAL4 driver drives transcription of UAS-trangenes in all eye disc cells posterior to the morphogenetic furrow[1,22]
Summary
EGF receptor acts through Ras and the MAPK cascade to trigger differentiation and maintain survival of most of cell types in the Drosophila retina. 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. The 'Second Mitotic Wave' plays no direct role in specifying or limiting cell fates, but is required to generate adequate numbers of retinal precursor cells[10,11]. It is not known why differentiation is normally restricted to G1 phase cells, given that eye discs contain cells at other cell cycle stages. Otherwise a mechanism is required to account for the inverse relationship between cell cycle progression and differentiation
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