Abstract
Regeneration after injury happens in a complex environment that requires precise orchestration of cell proliferation and establishment of correct patterning and cell-fate specification to ensure a fully functional outcome. Regenerative growth needs to be controlled and constrained to prevent overgrowth and to allow differentiation. However, the factors that are required to restrict regeneration to facilitate patterning of the regenerating tissue and establishment of correct cell fates have not been identified. Using a genetic ablation system in the Drosophila wing imaginal disc, we have identified the gene brain tumor (brat) as a protective factor that shields the regenerating tissue from excessive pro-growth gene activation and enables correct patterning and cell-fate specification. Regenerating discs with reduced levels of brat are unable to pattern correctly resulting in adult wings with a disrupted wing margin. This mis-patterning is due to elevated levels of the pro-growth factor Myc and the self-renewal factor Chinmo, which lead to suppression of the cell fate-specification gene cut (ct). Thus, Brat protects regenerating tissue from erroneous patterning by constraining expression of pro-regeneration genes.