Regulation of cell proliferation and wing development by Drosophila SIN3 and String

The transcriptional corepressor SIN3 is an essential gene in metazoans. In cell culture experiments, loss of SIN3 leads to defects in cell proliferation. Whether and how SIN3 may regulate the cell cycle during development has not been explored. To gain insight into this relationship, we have generated conditional knock down of Drosophila SIN3 and analyzed effects on growth and development in the wing imaginal disc. We find that loss of SIN3 affects normal cell growth and leads to down regulation of expression of the cell cycle regulator gene String (STG). A SIN3 knock down phenotype can be suppressed by overexpression either of STG or of Cdk1, the target of STG phosphatase. These data link SIN3 and STG in a genetic pathway that affects cell cycle progression in a developing tissue.