Switch and Trace: Recombinase Genetics in Zebrafish

Transgenic approaches are instrumental for labeling and manipulating cells and cellular machineries in vivo. Transgenes have traditionally been static entities that remained unaltered following genome integration, limiting their versatility. The development of DNA recombinase-based methods to modify, excise, or rearrange transgene cassettes has introduced versatile control of transgene activity and function. In particular, recombinase-controlled transgenes enable regulation of exogenous gene expression, conditional mutagenesis, and genetic lineage tracing. In zebrafish, transgenesis-based recombinase genetics using Cre/lox, Flp/FRT, and ΦC31 are increasingly applied to study development and homeostasis, and to generate disease models. Intersected with the versatile imaging capacity of the zebrafish model and recent breakthroughs in genome editing, we review and discuss past, current, and potential future approaches and resources for recombinase-based techniques in zebrafish.