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Endogenous OptoRhoGEFs reveal biophysical principles of epithelial tissue furrowing

Author

Listed:
  • Andrew D. Countryman

    (Columbia University)

  • Caroline A. Doherty

    (Princeton University
    Princeton University
    University of California)

  • R. Marisol Herrera-Perez

    (University of Rochester)

  • Karen E. Kasza

    (Columbia University)

Abstract

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.

Suggested Citation

  • Andrew D. Countryman & Caroline A. Doherty & R. Marisol Herrera-Perez & Karen E. Kasza, 2025. "Endogenous OptoRhoGEFs reveal biophysical principles of epithelial tissue furrowing," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62483-6
    DOI: 10.1038/s41467-025-62483-6
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    References listed on IDEAS

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