Eye Selector Logic for a Coordinated Cell Cycle Exit

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Organs develop from groups of undifferentiated cells that proliferate and differentiate into specific cell types. During development, the coupling between proliferation and differentiation programs ensures that enough cells of the different cell types are generated. This is critical for proper organ formation and function. Here, we use the developing Drosophila eye to examine how the coupling between these two programs is achieved. During eye development, progenitors are amplified before they exit the cell cycle and enter the differentiation program. This amplification step depends on an expression burst of the mitotic trigger string/cdc25, which, by forcing cells into mitosis, synchronizes cells in G1 just before differentiation onset. Thus string regulation acts as a hub where differentiation and proliferation programs are integrated. We identify a DNA element that controls the burst of string expression prior to differentiation, and show that it is regulated by the same gene network that triggers eye development. The transcription factor Pax6/Eyeless is a key regulator in this network. Eyeless acts cooperatively with Sine oculis and Eyes absent to regulate string, through a positive feed-forward loop. This loop is negatively modulated by the progenitor-specific transcription factor Homothorax/Meis1. This work shows that transcription factors that instruct cells to acquire an eye fate also control their proliferation regime, thus guaranteeing the coupling between proliferation and differentiation.

Vyšlo v časopise: Eye Selector Logic for a Coordinated Cell Cycle Exit. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004981
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004981

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