Epithelial Junction Dynamics in Developmental Biology

Epithelial tissues form selective barriers and undergo complex remodelling throughout embryogenesis and organogenesis. Central to these processes are specialised intercellular junctions—tight junctions, adherens junctions and their invertebrate counterparts, septate junctions—which coordinate cell polarity, adhesion and signal transduction. At the intersections of three cells, tricellular junctions provide additional mechanical reinforcement and regulate paracellular permeability. During tissue morphogenesis, junctional complexes dynamically assemble and disassemble in concert with the actomyosin cytoskeleton, enabling cell shape changes, intercalation and collective migration. Mechanical cues transmitted through junctions influence cell fate and patterning, while molecular modifications of junctional components modulate barrier function and tissue integrity. Studies across model organisms have revealed that junction dynamics underpin processes as varied as axis extension in Drosophila, anterior visceral endoderm migration in mouse embryos and multiciliated cell integration in amphibian epithelia. Insights into the regulation of cortical tension, junctional turnover and cell–junction crosstalk are critical for understanding congenital defects, epithelial repair and tumour progression, and provide guiding principles for tissue engineering and regenerative medicine.

Research from Nature Portfolio

Recent studies have revealed how mechanical forces at tricellular vertices shape epithelial organisation. Loss of a key adhesion molecule disrupts actomyosin homoeostasis, causing local concentration of contractile activity at tricellular contacts, displacement of tight junction belts and compromised monolayer integrity. Pharmacological inhibition of myosin-II restores uniform cortical tension, highlighting the importance of balanced force distribution for epithelial cohesion. Complementary work in Xenopus embryos has shown that multiciliated cell precursors extend filopodia to probe the stiffness of the overlying epithelial sheet. These filopodial pulls identify permissive sites for cell insertion and actively remodel neighbouring junctions, creating gaps through which cells integrate. Together, these findings uncover previously unrecognised roles for junction–cytoskeleton feedback and mechanical probing in orchestrating cell integration and preserving barrier function during development.

Epithelial Junction Dynamics in Developmental Biology publication trend

The graph below shows the total number of articles in epithelial junction dynamics in developmental biology across all publications each year (not limited to Nature Index journals).

Technical terms

Tight junction: A multiprotein complex sealing the space between adjacent epithelial cells, regulating paracellular transport and maintaining polarity.

Adherens junction: A cadherin–catenin‐based adhesion complex linking the actin cytoskeleton of neighbouring cells, crucial for tissue integrity and mechanotransduction.

Septate junction: The invertebrate functional analogue of vertebrate tight junctions, forming an occluding barrier in Drosophila epithelia.

Tricellular junction: A specialised structure at the meeting point of three cells, providing additional mechanical support and barrier function.

Actomyosin network: A contractile fibre system of actin filaments and myosin motors that generates tension at cell junctions and drives shape changes.

Filopodia: Thin, actin‐rich protrusions that extend from cells to sense mechanical properties of the environment and guide migration or integration.

Palmitoylation: A reversible lipid modification of proteins that enhances membrane association and regulates subcellular localisation and function.

Cell intercalation: The rearrangement of cells within a tissue where neighbours exchange contacts, enabling tissue elongation or narrowing.

References

1. Palmitoylation of proteolipid protein M6 promotes tricellular junction assembly in epithelia of Drosophila. Journal of Cell Science (2024).
2. Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity. Nature Communications (2017).
3. Multiciliated cells use filopodia to probe tissue mechanics during epithelial integration in vivo. Nature Communications (2022).
4. Multi-Cellular Rosettes in the Mouse Visceral Endoderm Facilitate the Ordered Migration of Anterior Visceral Endoderm Cells. PLOS Biology (2012).
5. The tricellular vertex-specific adhesion molecule Sidekick facilitates polarised cell intercalation during Drosophila axis extension. PLOS Biology (2019).