A noninvasive photoactivatable split-Cre recombinase system for genome engineering in zebrafish

The cyclic recombinase (Cre)/loxP recombination system is a powerful technique for in vivo cell labeling and tracking. However, achieving high spatiotemporal precision in cell tracking using this system is challenging due to the requirement for reliable tissue-specific promoters. In contrast, light-inducible systems offer superior regional confinement, tunability, and non-invasiveness compared to conventional lineage-tracing methods. Here, we took advantage of the unique strengths of the zebrafish to develop an easy-to-use highly efficient, genetically encoded, magnets-based, light-inducible transgenic Cre/loxP system. We demonstrate that our system does not exhibit phototoxicity or leakiness in the dark, and it enables efficient and robust Cre/loxP recombination in various tissues and cell types at different developmental stages through noninvasive illumination with blue light. Our newly developed tool is expected to open novel opportunities for light-controlled tracking of cell fate and migration in vivo.