During development, cell fate is specified by sequential recruitment of genes. The fate of Drosophila imaginal discs can be redirected when discs regenerate or when key genes are mis-regulated. Here, Justin Kumar and colleagues demonstrate that the epigenetic factor Polycomb plays a role in establishing the fate of the Drosophila eye disc. First, the authors show that when Polycomb expression is reduced, the eye disc transforms into a wing disc due to ectopic activation of vestigial, the key gene for wing specification. The authors find that ectopic Vestigial forms a complex with Scalloped, its binding partner in the wing disc. They suggest that reducing Polycomb expression in the eye recreates the genetic conditions normally found in the wing disc, forcing the eye to transform into a wing. Furthermore, the authors show that disrupting this Vestigial-Scalloped complex while simultaneously reducing Polycomb expression in the eye disc does not block wing formation or revert to its original eye fate. Instead, they observe overgrowth and re-specification into other imaginal discs. RNA-sequencing profiles of these overgrown discs suggest heterogeneity of cells reminiscent of human tumours. Overall, the findings provide mechanistic insight into how Polycomb promotes eye fate and, more generally, its role in tissue fate specification.
