PUBLICATION
zHORSE as an optogenetic zebrafish strain for precise spatiotemporal control over gene expression during development
- Authors
- Varady, A., Grissenberger, S., Fischer, K., Stadler, M.T., Wenninger-Weinzierl, A., Strobl, M., Zila, N., Kovar, H., Distel, M.
- ID
- ZDB-PUB-250628-13
- Date
- 2025
- Source
- Developmental Cell : (Journal)
- Registered Authors
- Distel, Martin, Fischer, Kristin, Grissenberger, Sarah, Stadler, Manuela, Varady, Adam, Wenninger-Weinzierl, Andrea
- Keywords
- EWS::FLI1, fin formation, gene expression, optogenetics, recombinase, synthetic biology, zebrafish
- MeSH Terms
-
- Animal Fins/metabolism
- Animals
- Animals, Genetically Modified
- Cell Lineage
- Gene Expression Regulation, Developmental*/genetics
- Integrases/genetics
- Integrases/metabolism
- Optogenetics*/methods
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 40578366 Full text @ Dev. Cell
Citation
Varady, A., Grissenberger, S., Fischer, K., Stadler, M.T., Wenninger-Weinzierl, A., Strobl, M., Zila, N., Kovar, H., Distel, M. (2025) zHORSE as an optogenetic zebrafish strain for precise spatiotemporal control over gene expression during development. Developmental Cell. :.
Abstract
Proper vertebrate development is dependent on tightly regulated expression of genes at the correct time and place. To identify normal but also dysregulated development leading to disease, in vivo interrogation methods with high spatiotemporal resolution are required. Recently, optogenetic tools to manipulate gene expression with spatiotemporal control have emerged, but their in vivo applications remain challenging. Here, we present a transgenic zebrafish strain termed zebrafish for heat-shock-inducible optogenetic recombinase expression (zHORSE) with inducible expression of a light-activatable Cre recombinase. We demonstrate that zHORSE endows robust spatiotemporal control over gene expression down to single-cell level at different developmental stages. We apply zHORSE for lineage tracing to identify caudal fin progenitors and for targeted expression of oncogenes. Surprisingly, one oncogene, EWS::FLI1, can cause ectopic fin formation when induced in permissive environments. zHORSE is compatible with existing loxP zebrafish effector strains and will enable many applications ranging from dissecting and precisely manipulating development to clonal cancer modeling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping