Precise temporal control of gene expression is a prerequisite for disentangling timing-specific effects of gene function within the life cycle of Drosophila melanogaster. Here, we implement light-inducible FLPase reconstitution (LIFR) as a conditional gene expression system in flies, which combines blue light-responsive Magnet photoswitches and split-FLPase to remove an FRT-flanked stop cassette and irreversibly switch on transgene expression in response to light. This system is highly efficient, has virtually no transgene leakage, and a single light pulse is sufficient to induce long-term transgene expression. We demonstrate that LIFR in adulthood overcomes the developmental lethality elicited by constitutive pan-neuronal overexpression of neurodegeneration-causing mutants TDP43G298S and HTTQ97. We also illustrate that LIFR can help trace specific cell-type fates across developmental stages. Thus, we demonstrate proof of principle that LIFR is a versatile platform to conditionally activate long-lasting gene expression without the side effects of existing systems, thereby extending the Drosophila melanogaster genetic toolbox.
Shridharan et al. (2026) studied this question.