Antagonistic regulation of the second mitotic wave by Eyes absent-Sine oculis and Combgap coordinates proliferation and specification in the Drosophila retina

The transition from proliferation to specification is fundamental to the development of appropriately patterned tissues. In the developing Drosophila eye, Eyes absent (Eya) and Sine oculis (So) orchestrate the progression of progenitor cells from asynchronous cell division to G(1) arrest and neuronal specification at the morphogenetic furrow. Here, we uncover a novel role for Eya and So in promoting cell cycle exit in the second mitotic wave (SMW), a synchronized, terminal cell division that occurs several hours after passage of the furrow. We show that Combgap (Cg), a zinc-finger transcription factor, antagonizes Eya-So function in the SMW. Based on the ability of Cg to attenuate Eya-So transcriptional output in vivo and in cultured cells and on meta analysis of their chromatin occupancy profiles, we speculate that Cg limits Eya-So activation of select target genes posterior to the furrow to ensure properly timed mitotic exit. Our work supports a model in which context-specific modulation of transcriptional activity enables Eya and So to promote both entry into and exit from the cell cycle in a distinct spatiotemporal sequence.