Calcium and actomyosin pulses drive tricellular zipping to remodel epithelial cell-cell junctions and facilitate cell packing
- 1University of Michigan, Ann Arbor, MI, USA
Abstract
Epithelial morphogenesis requires coordinated changes in cell geometry, neighbor cell arrangement, and cell packing to generate functional tissue architectures. However, the spatiotemporal regulation of upstream signals that drive local junctional remodeling in highly proliferative developing epithelial tissues remains unclear. Here, we characterize a new junction remodeling process, which we call "tricellular zipping". It resolves long, thin cell extensions generated by cell-division forces that terminate at transient higher-order vertices. We show that tricellular zipping facilitates epithelial cell packing in blastula-stage Xenopus laevis embryos through asymmetric displacement of a tricellular vertex and formation of a de novo bicellular interface. Similarly, we observe tricellular zipping in developing mouse embryos. Combining modeling and live imaging approaches, we find that displacement of the remodeling vertex depends on actomyosin-dependent asymmetric force generation and on enrichment of adaptor proteins coupling actomyosin to junctions, which enables effective force transmission. In contrast, the stationary vertex remains close to mechanical equilibrium and therefore undergoes no net displacement. Furthermore, we find that calcium flashes drive the localized, pulsatile actomyosin contractility required for efficient tricellular zipping. Extending our observations, we show that disrupting transient calcium signaling also affects cell packing in Drosophila embryos, thereby impairing mesoderm internalization. Overall, by combining multidisciplinary and multisystem approaches, we uncover a new mode of junctional remodeling and highlight the importance of spatiotemporally regulated calcium signaling in driving local junctional rearrangements to facilitate morphogenesis.
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BibTeX
@misc{adhikary2026calcium,
title = {{Calcium and actomyosin pulses drive tricellular zipping to remodel epithelial cell-cell junctions and facilitate cell packing}},
author = {B. Adhikary and X. O. Zhao and A. Shahi and A. G. Laboy-Figueroa and M. P. Purvis and K. K. Tjoelker and T. R. Huycke and S. Banerjee and A. C. Martin and A. L. Miller},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.763104},
url = {https://www.biorxiv.org/content/10.64898/2026.10.30.763104v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Calcium and actomyosin pulses drive tricellular zipping to remodel epithelial cell-cell junctions and facilitate cell packing
AU - B. Adhikary
AU - X. O. Zhao
AU - A. Shahi
AU - A. G. Laboy-Figueroa
AU - M. P. Purvis
AU - K. K. Tjoelker
AU - T. R. Huycke
AU - S. Banerjee
AU - A. C. Martin
AU - A. L. Miller
PY - 2026
DA - 2026/10/30
PB - bioRxiv
DO - 10.64898/2026.10.30.763104
UR - https://www.biorxiv.org/content/10.64898/2026.10.30.763104v1
AB - Epithelial morphogenesis requires coordinated changes in cell geometry, neighbor cell arrangement, and cell packing to generate functional tissue architectures. However, the spatiotemporal regulation of upstream signals that drive local junctional remodeling in highly proliferative developing epithelial tissues remains unclear. Here, we characterize a new junction remodeling process, which we call "tricellular zipping". It resolves long, thin cell extensions generated by cell-division forces that terminate at transient higher-order vertices. We show that tricellular zipping facilitates epithelial cell packing in blastula-stage Xenopus laevis embryos through asymmetric displacement of a tricellular vertex and formation of a de novo bicellular interface. Similarly, we observe tricellular zipping in developing mouse embryos. Combining modeling and live imaging approaches, we find that displacement of the remodeling vertex depends on actomyosin-dependent asymmetric force generation and on enrichment of adaptor proteins coupling actomyosin to junctions, which enables effective force transmission. In contrast, the stationary vertex remains close to mechanical equilibrium and therefore undergoes no net displacement. Furthermore, we find that calcium flashes drive the localized, pulsatile actomyosin contractility required for efficient tricellular zipping. Extending our observations, we show that disrupting transient calcium signaling also affects cell packing in Drosophila embryos, thereby impairing mesoderm internalization. Overall, by combining multidisciplinary and multisystem approaches, we uncover a new mode of junctional remodeling and highlight the importance of spatiotemporally regulated calcium signaling in driving local junctional rearrangements to facilitate morphogenesis.
ER -