Planar Cell Polarity Mechanisms in Developmental Biology

Planar cell polarity (PCP) describes the coordinated orientation of cells across the tissue plane, a fundamental feature of epithelial and mesenchymal morphogenesis. Central to PCP are two conserved molecular modules: the core pathway, comprising factors such as Frizzled, Dishevelled and Van Gogh/Vangl, and the Fat–Dachsous system, which interprets graded expression cues to bias cell polarity. These modules establish subcellular asymmetries through intercellular complexes and directional trafficking of components, thereby directing processes from convergent extension in gastrulation to orientation of sensory hair cells and neural tube closure. Non-canonical Wnt ligands and G protein signals converge on the PCP machinery to refine directional information, while cytoskeletal effectors such as Rho‐associated kinase and myosin II translate polarity cues into force generation and cell-shape change. Disruption of PCP leads to defects in organogenesis, including neural tube defects, congenital heart malformations and sensory dysfunction. Beyond development, aberrant PCP signalling has been implicated in tumour progression and tissue regeneration, underscoring its clinical relevance. Recent advances have elucidated how extracellular ligands, atypical cadherins and scaffold proteins integrate to regulate the assembly, stability and orientation of PCP complexes, providing a unified view of how global and local cues orchestrate tissue patterning and function.

Research from Nature Portfolio

Recent studies have defined a multi-protein complex that instructs apical constriction during neural tube formation. Wnt4 and the transmembrane ligand ephrinB2 form a signalling assembly with Ror2, Dishevelled and Shroom3, termed WERDS, which activates Rho-associated kinase to drive cytoskeletal contractility and membrane deformation. This work reveals cross-talk between non-canonical Wnt and Eph/ephrin pathways, clarifying how cells coordinate morphogenetic movements. In a complementary advance, overexpression of the core PCP component VANGL2 in basal breast cancers has been linked to a proliferative signalling cascade via the scaffold p62/SQSTM1 and JNK activation. Disruption of the VANGL2–p62 interaction or inhibition of JNK attenuates tumour cell growth, demonstrating how non-canonical Wnt–PCP effectors can be co-opted in malignancy and presenting novel therapeutic targets.

Planar Cell Polarity Mechanisms in Developmental Biology publication trend

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

Technical terms

Planar cell polarity (PCP): The coordinated orientation of cells within the plane of a tissue, essential for tissue morphogenesis.

Non-canonical Wnt signalling: A Wnt pathway that regulates cell movement and polarity rather than gene transcription.

Apical constriction: The process by which cells shrink their apical surface to drive tissue folding.

Cadherins: Calcium-dependent adhesion proteins that mediate cell–cell junctions and polarity.

Inhibitory G proteins (Gαi): GTP-binding proteins that transduce signals to regulate cell polarity and morphogenesis.

References

1. Wnt4 and ephrinB2 instruct apical constriction via Dishevelled and non-canonical signaling. Nature Communications (2023).
2. Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2–JNK signalling in breast cancer. Nature Communications (2016).
3. Fat-Dachsous planar polarity function requires two distinct heterophilic cadherin-cadherin binding interactions. Cell Reports (2024).
4. Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis. eLife (2024).