Port, F. et al. Elife 9, e53865 (2020).

CRISPR screens have become a valuable tool for interrogating gene function in mammalian cells. In vivo CRISPR screens typically rely on tight temporal and spatial control of mutagenesis, which remains a challenge. Port et al. describe and characterize a single guide RNA (sgRNA) library for tissue-specific CRISPR screening in Drosophila. Currently, tissue-specific expression of transgenes is often enabled by the Gal4–UAS system in Drosophila. In this work, the researchers use UAS-Cas9 transgenes and a sgRNA expression vector (pCFD6) to attain Gal4-dependent CRISPR mutagenesis. They demonstrate this conditional CRISPR mutagenesis in somatic tissues, such as imaginal discs, and in the germline. Overall, the resource consists of around 2,600 plasmids and 1,700 fly lines, mainly covering functional gene groups such as kinases, phosphatases and transcription factors. These transgenic fly lines and the plasmids will be publically available.