Epithelial Morphogenesis and Cell Polarity Dynamics

Epithelial tissues define organ boundaries and perform selective barrier, transport and signalling functions. Their formation relies on the orchestration of cell polarisation, coordinated shape changes and controlled cavity formation. Apico-basal polarity establishes distinct apical and basolateral domains through asymmetric distribution of lipids, protein complexes and cytoskeletal elements. Morphogenetic processes such as epithelial thinning, cell rearrangements and lumenogenesis generate three-dimensional architectures in organs from kidney tubules to inner-ear vesicles. Mechanical forces driven by actomyosin contractility, hydrostatic pressure and extracellular matrix interactions integrate with biochemical and bioelectrical cues to shape tissue dimensions and ensure robust development. Dysregulation of polarity or morphogenesis underlies a spectrum of congenital and acquired disorders, emphasising the importance of understanding dynamic cell and tissue-scale interactions.

Research from Nature Portfolio

Recent studies have demonstrated that physiological-strength electrical stimulation can directly modulate tissue shape and size through a process termed electro-inflation. By applying external fields to three-dimensional organoid models, researchers showed that ion flux across epithelial membranes drives osmotic water influx, creating hydrostatic pressure within luminal cavities that competes with cytoskeletal tension and induces symmetry breaking and shape change. Separately, molecular dissection of polarity initiation revealed that a specific Rab GTPase tethers apical-determinant-bearing vesicles at the midbody during the first cell division, coupling cytokinesis to the onset of apico-basal polarity and central lumen opening. Foundational work on cortical lipid asymmetry uncovered an apical identity determinant in the form of a phosphoinositide species, which is produced and localised by specific kinases and phosphatases to guide endosomal trafficking and membrane domain establishment during early polarisation.

Epithelial Morphogenesis and Cell Polarity Dynamics publication trend

The graph below shows the total number of articles in epithelial morphogenesis and cell polarity dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Apico-basal polarity: Organisation of epithelial cells into apical (facing lumen) and basolateral (contacting extracellular matrix) domains.

Lumenogenesis: Formation of a fluid-filled cavity within an epithelial structure through cell polarisation and membrane trafficking.

Tight junctions: Intercellular protein complexes that seal adjacent epithelial cells, regulate paracellular transport and contribute to mechanical integrity.

Hydrostatic pressure: Force generated by fluid accumulation within a closed cavity, which influences tissue shape and mechanical balance.

Electro-inflation: Bioelectric modulation of epithelial lumen expansion via applied electrical fields that drive ion-mediated osmotic swelling.

References

1. Mitotic cell rounding and epithelial thinning regulate lumen growth and shape. Nature Communications (2015).
2. Collective Cell Migration Drives Morphogenesis of the Kidney Nephron. PLOS Biology (2009).
3. Size control of the inner ear via hydraulic feedback. eLife (2019).
4. Bioelectric stimulation controls tissue shape and size. Nature Communications (2024).
5. Rab35 GTPase couples cell division with initiation of epithelial apico-basal polarity and lumen opening. Nature Communications (2016).
6. The phospholipid PI(3,4)P2 is an apical identity determinant. Nature Communications (2018).
7. Tight junctions control lumen morphology via hydrostatic pressure and junctional tension. Developmental Cell (2024).