RESEARCH ARTICLE Eye Selector Logic for a Coordinated Cell Cycle Exit

Organ-selector transcription factors control simultaneously cell differentiation and prolifera-tion, ensuring the development of functional organs and their homeostasis. How this is achieved at the molecular level is still unclear. Here we have investigated how the transcrip-tional pulse of string/cdc25 (stg), the universal mitotic trigger, is regulated during Drosophila retina development as an example of coordinated deployment of differentiation and prolifer-ation programs. We identify the eye specific stg enhancer, stg-FMW, and show that Pax6 selector genes, in cooperation with Eya and So, two members of the retinal determination network, activate stg-FMW, establishing a positive feed-forward loop. This loop is negatively modulated by the Meis1 protein, Hth. This regulatory logic is reminiscent of that controlling the expression of differentiation transcription factors. Our work shows that subjecting tran-scription factors and key cell cycle regulators to the same regulatory logic ensures the cou-pling between differentiation and proliferation programs during organ development. Author Summary Organs develop from groups of undifferentiated cells that proliferate and differentiate int