While genetic screens are a powerful tool for identifying novel genes involved in complex biological processes, traditional screening methods in Drosophila, including the popular RNAi strategy, hold various limitations. We have established and optimized a novel screening strategy, using a variation of the CRISPR/Cas9 technology, referred to as tissue-specific (ts)CRISPR. tsCRISPR enables precise targeting of any desired gene in a specific tissue or population of cells, within a single cross (10 days!). Being simple and fast, tsCRISPR is ideal for high-throughput in vivo screening. Using optimized tools, our lab has generated a large-scale resource of gRNA-expressing plasmids and fly lines targeting hundreds of Drosophila genes, which is available to the worldwide fly community. Our gRNA-collection can be readily used for large-scale screening in any Drosophila tissue or organ. In the mushroom body, it allowed the identification of many novel genes involved in neuronal remodeling.
