Endogenous OptoRhoGEFs reveal biophysical principles of epithelial tissue furrowing
During development, epithelia function as malleable sheets that undergo extensive remodeling to shape developing embryos. Optogenetic control of Rho signaling provides an avenue to investigate mechanisms of epithelial morphogenesis, but transgenic optogenetic tools can be limited by variability in expression levels and deleterious effects of transgenic overexpression on development. Here, we use CRISPR/Cas9 to tag Drosophila RhoGEF2 and Cysts/Dp114RhoGEF with components of the iLID/SspB optogenetic heterodimer, permitting light-dependent control over endogenous protein activities. Using quantitative optogenetic perturbations, we uncover a dose-dependence of tissue furrow depth and bending behavior on RhoGEF recruitment, revealing mechanisms by which developing embryos can shape tissues into particular morphologies. We show that at the onset of gastrulation, furrows formed by cell lateral contraction are oriented and size-constrained by basal actomyosin. Our findings demonstrate the use of quantitative, 3D-patterned perturbations of cell contractility to precisely shape tissue structures and interrogate developmental mechanics.
Authors
- Karen E. Kasza (ORCID: https://orcid.org/0000-0002-0888-3579)
- Caroline A. Doherty
- R. Marisol Herrera-Perez (ORCID: https://orcid.org/0000-0001-8346-5185)
- Andrew D. Countryman (ORCID: https://orcid.org/0000-0002-0377-8075)
Institutions
- Princeton University (US)
- Broad Center (US)
- University of Rochester (US)
- Columbia University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-18
- DOI
- https://doi.org/10.1038/s41467-025-62483-6
- Primary Topic
- Advanced Fluorescence Microscopy Techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- David and Lucile Packard Foundation
- Alfred P. Sloan Foundation
- City University of New York
- National Institutes of Health
- National Institute of General Medical Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development