Epithelial Polarity Mechanisms in Cell Morphogenesis

Epithelial polarity underpins the organised architecture of tissues, directing the asymmetric distribution of proteins, lipids and cytoskeletal elements along the apical–basal axis. This spatial segregation is driven by conserved polarity complexes—including the Par, Crumbs and Scribble modules—which coordinate assembly of tight and adherens junctions at defined membrane domains. Reciprocal antagonism between apical and basolateral determinants, regulated by kinases such as atypical protein kinase C (aPKC), establishes sharp cortical boundaries that sculpt cell shape and organise lumen formation. Recent advances reveal that phase‐separated protein condensates contribute to mesoscale patterning at membrane interfaces, while transcriptional and epigenetic control of junctional components fine-tunes polarity across developmental and pathological contexts. Cytoskeletal polarisation, orchestrated by microtubule-binding proteins and motor complexes, ensures targeted delivery of vesicles to apical or basolateral surfaces, thereby reinforcing domain identity. Together, these mechanisms translate molecular asymmetries into coordinated cell morphology, driving epithelial tube formation, barrier function and organogenesis with broad implications for understanding disease states arising from polarity disruption.

Research from Nature Portfolio

Recent studies have shown that biomolecular condensates can ‘wet’ membrane interfaces to drive tight-junction belt formation. In this model, a polarity scaffold promotes condensation of junctional proteins into a contiguous apical layer, with the kinetics of belt formation dictated by interfacial binding affinities. Mutational analyses demonstrate that altering protein–membrane interactions is sufficient to modulate belt elongation, revealing a physical basis for junction assembly. Complementary structural work on the aPKC–Par6–Lgl axis has elucidated a capture-and-release mechanism by which the basolateral substrate Lgl binds the kinase complex in a phospho-intermediate state. This assembly inhibits further phosphorylation until cues from active Cdc42 and Crumbs trigger complex disassembly, thereby spatially controlling kinase activity and reinforcing domain segregation at the apical boundary.

Epithelial Polarity Mechanisms in Cell Morphogenesis publication trend

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

Technical terms

Apical–basal polarity: Asymmetric organisation of cellular domains along the axis from the lumen-facing apical surface to the basement-attached basal surface.

Biomolecular condensates: Membraneless, phase-separated protein assemblies that compartmentalise and concentrate factors at distinct cellular sites.

Tight junctions: Multi-protein complexes that seal the apical regions of adjacent epithelial cells to control paracellular transport.

Par complex: A polarity determinant comprising Par3, Par6 and aPKC that defines apical membrane identity.

Lethal giant larvae (Lgl): A basolateral polarity substrate whose phosphorylation state regulates its cortical localisation.

Hippo signalling pathway: A kinase cascade that regulates cell proliferation and organ size, interacting with polarity proteins to control cytoskeletal dynamics.

Vertebrate marginal zone (VMZ): A distinct membrane compartment apical of tight junctions defined by the Crumbs–Pals1–PatJ complex.

References

1. Membrane prewetting by condensates promotes tight-junction belt formation. Nature (2024).
2. Capture, mutual inhibition and release mechanism for aPKC–Par6 and its multisite polarity substrate Lgl. Nature Structural & Molecular Biology (2025).
3. PATJ inhibits histone deacetylase 7 to control tight junction formation and cell polarity. Cellular and Molecular Life Sciences (2023).
4. The Mammalian Crumbs Complex Defines a Distinct Polarity Domain Apical of Epithelial Tight Junctions. Current Biology (2020).
5. Shot and Patronin polarise microtubules to direct membrane traffic and biogenesis of microvilli in epithelia. Journal of Cell Science (2016).