zHORSE as an optogenetic zebrafish strain for precise spatiotemporal control over gene expression during development

Area of Science:

• Developmental Biology
• Genetics
• Optogenetics

Background:

• Vertebrate development requires precise gene regulation.
• In vivo methods with high spatiotemporal resolution are needed to study development and disease.
• Optogenetic tools offer spatiotemporal control but face in vivo challenges.

Purpose of the Study:

• To develop a novel transgenic zebrafish model for inducible optogenetic control of gene expression.
• To demonstrate the utility of this model for high-resolution lineage tracing and gene manipulation in vivo.
• To explore the effects of oncogene expression during development.

Main Methods:

• Creation of a transgenic zebrafish strain (zHORSE) for heat-shock-inducible optogenetic recombinase expression.
• Utilizing light-activatable Cre recombinase for spatiotemporal gene expression control.
• Application of zHORSE for lineage tracing of caudal fin progenitors and targeted oncogene expression.

Main Results:

• zHORSE provides robust spatiotemporal control over gene expression at the single-cell level across developmental stages.
• Lineage tracing identified caudal fin progenitors.
• Induction of the EWS::FLI1 oncogene led to surprising ectopic fin formation.

Conclusions:

• The zHORSE system offers precise spatiotemporal control for studying vertebrate development and disease.
• This model facilitates applications in developmental biology, lineage tracing, and clonal cancer modeling.
• The study uncovered an unexpected developmental role for the EWS::FLI1 oncogene.