Biology subjects

Huycke, T. R.

Publications and source records attributed to Huycke, T. R..

3 recordsLinked to original sources

bioRxiv2026

Calcium and actomyosin pulses drive tricellular zipping to remodel epithelial cell-cell junctions and facilitate cell packing

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.

cell biology↗

bioRxiv2023

Patterning and folding of intestinal villi by active mesenchymal dewetting

Tissue folding generates structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, the numerous finger-like protrusions that are essential for nutrient absorption. However, the molecular and mechanical mechanisms driving the initiation and morphogenesis of villi remain a matter of debate. Here, we identify an active mechanical mechanism that simultaneously patterns and folds intestinal villi. We find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. At the cell-level, this occurs through a process dependent upon matrix metalloproteinase-mediated tissue fluidization and altered cell-ECM adhesion. By combining computational models with in vivo experiments, we reveal these cellular features manifest at the tissue-level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active de-wetting of a thin liquid film.

developmental biology↗

bioRxiv2023

Hox genes modulate physical forces to differentially shape small and large intestinal epithelia

The small and large intestines arise from a common primordial gut tube but ultimately become specialized in both form and function. While the midgut forms villi, the hindgut develops flat, brain-like sulci that resolve into heterogeneous outgrowths. Gut compartment identities are demarcated early in development via Hox genes, which are highly conserved, master regulators of spatial patterning in the embryo. Yet, how these factors trigger regional morphogenesis has remained a mystery. Combining mechanical measurements and mathematical modeling, we demonstrate that the posterior Hox gene Hoxd13 regulates biophysical phenomena that shape the hindgut lumen. We further show that Hoxd13 acts through the TGF{beta} pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme; together, these features generate hindgut surface patterns. TGF{beta}, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of genetic identity that direct posterior intestinal morphogenesis.

developmental biology↗