Vertebrates exhibit a bilaterally symmetric body plan while developing left–right (LR) asymmetric internal organs (Martindale et al., 2002; Namigai et al., 2014). Such bilaterality is established and maintained by the midline, which defines the LR axis and coordinates patterning with the anterior–posterior (AP) and dorsal–ventral (DV) axes (Meinhardt, 2006; Bénazéraf and Pourquié, 2013). Subsequent LR laterality along the midline is specified by asymmetric expression of LR regulatory genes, including sonic hedgehog (Shh) and nodal (Levin et al., 1995; Tabin, 2006). Disruption of midline formation or errors in LR patterning can result in congenital disorders such as heterotaxy (Aylsworth, 2001; Ramsdell et al., 2006; Deng et al., 2015). Although the midline is widely conserved among bilaterians and is indispensable for establishing the bilateral body plan, the mechanisms that build and stabilize this axis remain incompletely understood.

A major molecular mechanism coordinating midline morphogenesis across vertebrates is the Wnt/Planar cell polarity (PCP) pathway, an evolutionarily conserved non-canonical Wnt signaling pathway that coordinates cytoskeletal remodeling and oriented cell behaviors, thereby establishing planar polarization within tissues (Yang and Mlodzik, 2015). In gastrulation, Wnt/PCP links molecular polarity to collective cell behaviors that contribute to shaping the emerging midline (Tada et al., 2002; Voiculescu et al., 2007; Roszko et al., 2009).

One prominent Wnt/PCP-dependent collective behavior is convergent extension (CE), the coordinated narrowing and elongation of tissues driven largely by mediolateral intercalation and other polarized rearrangements (Keller et al., 2000). In vertebrates, core PCP components become asymmetrically organized within cells, and disruption of PCP signaling, including by dominant-negative Dishevelled (Dvl) constructs that selectively impair PCP, compromises CE in frog and avian systems (Sokol, 1996; Wallingford et al., 2000; Voiculescu et al., 2007). Mechanistically, PCP engages Rho–ROCK and related small-GTPase pathways to organize actin dynamics and contractility; consistent with this, PCP inhibition can block stable bipolar protrusions in Xenopus notochord cells and arrest tissue elongation (Wallingford et al., 2002; Shindo, 2018). Overall, the Wnt/PCP pathway regulates CE by polarizing protrusive and junctional behaviors and coupling these cell-scale processes to tissue-scale morphogenetic processes, thereby promoting midline formation.

Midline formation begins during gastrulation, a stage characterized by large-scale cellular flows (extensive collective cell movements). In non-amniotes (e.g., fish and amphibians), midline morphogenesis is tightly coupled to these flows, and Wnt/PCP-mediated planar polarization provides a mechanistic basis for this coupling through CE and tissue elongation (Keller et al., 2000; Tada et al., 2002; Roszko et al., 2009). This tight coupling offers a relatively direct framework for connecting pathway activity to tissue-level morphogenesis.

By contrast, amniotes establish the earliest midline structure through the primitive streak (PS) in an epithelial epiblast, most prominently characterized in avian embryos (Mikawa et al., 2004). The Wnt/PCP pathway is essential for PS morphogenesis and extension (Voiculescu et al., 2007; Asai et al., 2024), yet how it contributes to the accompanying cellular flows during PS development has yet to be fully elucidated. Existing perturbation and quantitative imaging studies indicate that key aspects of tissue-scale flows can persist even when PS morphology is compromised (Asai et al., 2024), underscoring the need for systematic, quantitative tests of how PCP activity relates to flow parameters and to early LR bias prior to a mature organizer.

Accordingly, this Mini Review integrates historical and recent findings on Wnt/PCP in non-amniote and amniote gastrulation, highlights conserved mechanisms and species-specific developmental processes, and outlines testable hypotheses for how Wnt/PCP interfaces with cellular flows to establish the vertebrate body plan. We emphasize where evidence supports tight coupling, where it instead points to partial decoupling, and which quantitative measurements are needed to resolve the remaining open questions.

The Wnt/PCP pathway has been extensively studied as a conserved planar polarity machinery that is redeployed in distinct tissue contexts to bias cell behaviors and thereby organize morphogenesis. Core PCP components include Frizzled (Fz), Van Gogh-like (Vangl), Flamingo/Celsr, Prickle (Pk), and Dvl (Wansleeben and Meijlink, 2011; Gao, 2012; Davey and Moens, 2017). Through intercellular feedback and asymmetric subcellular distributions, PCP establishes planar polarity fields that can be read out by cytoskeletal regulators and junctional remodeling (Seifert and Mlodzik, 2007; Koca et al., 2022). In vertebrate development, PCP-dependent outputs include mediolateral intercalation, oriented cell elongation, and epithelial rearrangements that underlie convergent extension (Roszko et al., 2009).

Importantly, PCP acts within a broader tissue context. In some model animals, large-scale cellular flows appear to emerge as integrated outcomes of PCP-biased cell rearrangements (Tada and Smith, 2000; Wallingford et al., 2000; Matsui et al., 2005). In others, coherent flows can arise at the epithelium scale and are then shaped, or only partially constrained, by PCP-dependent remodeling (Asai et al., 2024; Zhao et al., 2025). Distinguishing between these regimes is essential for a comparative understanding of gastrulation in non-amniotes and amniotes. In this view, PCP translates molecular asymmetries into polarized cell behaviors that can scale up to coordinated tissue-level movements.

A conserved principle across vertebrates is that Wnt/PCP provides a PCP module that biases cell behaviors (e.g., cell rearrangement, cell-shape changes, and cell division), in many contexts, supports tissue-scale morphogenesis and flow (Keller et al., 2000; Myers et al., 2002). The species-specific implementation of this module becomes especially clear during amniote gastrulation, where the earliest midline is built through the PS within the epiblast cell layer. In this amniote context, recent findings on pre-node LR asymmetry associated with polonaise movements in the early chick embryo indicate that tissue-scale cellular flows can provide an early physical readout of laterality upstream of a robust organizer-centric gene program (Asai et al., 2025). However, during amniote PS development, the relative contributions of PCP-regulated local remodeling and epiblast-wide tissue context to flow organization, stability, and asymmetry remain unresolved. Addressing this amniote-specific gap will require quantitative endpoints beyond PS length/width, including flow parameters and polarity readouts, together with stage-dependent analyses under graded PCP perturbations across PS initiation, extension, and the transition to post-PS stages.

Developmental architecture is a key determinant of how this conserved pathway should be interpreted across clades. In non-amniotes, Wnt/PCP-dependent CE often links PCP to axis elongation in a relatively direct manner (Wallingford et al., 2000; Matsui et al., 2005). In amniotes, by contrast, PS morphogenesis unfolds within an epithelial embryonic disc and coincides with prominent tissue-scale flows and stronger growth requirements, conditions that can partially decouple flow dynamics from specific morphogenetic outputs (Asai et al., 2024; Zhao et al., 2025). A central challenge in amniotes, therefore, is to identify which PCP outputs (e.g., junctional remodeling, CE directionality via directed intercalation, or biased cell division) dominate at particular stages of PS and post-PS midline development, and to determine how these outputs regulate key features of tissue-scale flows, including their organization, stability, and asymmetry.

Focusing on amniote development, this section summarizes current insights into how the Wnt/PCP pathway interfaces with PS morphogenesis, tissue-scale flows, and early LR patterning during gastrulation. In amniotes, these processes unfold within an epithelial embryonic disc and can show partial uncoupling between specific morphogenetic outputs, motivating stage-resolved interpretations of pathway function.

A key open question in amniote gastrulation is what is a driving force of the polonaise movements, and how the Wnt/PCP pathway relates to these processes. Cellular flow initiation can occur even when PS extension is compromised, implying that vortical flows do not strictly require PS morphogenesis (Cui et al., 2005; Asai et al., 2024; Asai et al., 2025). This points to upstream determinants acting at the epiblast scale, while leaving open the possibility that Wnt/PCP primarily refines or patterns these movements rather than serving as the sole trigger. A key next step is to define minimal requirements for sustained vortices using quantitative flow analysis combined with graded perturbations of PCP components, with staging that separates effects on PS geometry from effects on the flow field.

From an evolutionary perspective, these observations also motivate a layered model for early midline morphogenesis in amniotes. The PS represents an evolutionarily derived midline structure that was added to the vertebrate developmental program, and its extension may therefore incorporate a proliferation-dependent module in addition to the conserved Wnt/PCP-mediated CE machinery (Wei and Mikawa, 2000; Zhao et al., 2025). This framing helps reconcile stage-specific sensitivities: PS extension can be strongly affected by mitotic inhibition even when large-scale flows can still be initiated, consistent with partial uncoupling between streak morphogenesis and flow onset.

A second open question is when and how LR bias first appears within the polonaise movements. Quantitative analyses indicate that right-side dominance emerges reproducibly around ∼6 h after motion onset and can persist under mitotic arrest (Asai et al., 2025), placing detectable LR bias upstream of a mature organizer-centric gene program. Multiple mechanisms could underlie this bias, including intrinsic cellular chirality, subtle early molecular asymmetries, or an asymmetric tissue context. Discriminating among these possibilities will require sensitive mapping of LR differences in flow parameters and targeted perturbations to test whether the Wnt/PCP pathway contributes to bias formation, bias amplification, or the robustness of bias expression.

Placing these amniote-specific questions in a broader comparative context helps distinguish conserved principles from species-specific implementations of the Wnt/PCP pathway. In non-amniotes, Wnt/PCP-dependent CE and axial/midline elongation are often more tightly coupled, providing a relatively direct link between planar polarity at the cellular level and tissue-scale axis extension. In amniotes, by contrast, primitive streak morphogenesis occurs within a disc-shaped epiblast alongside prominent tissue-scale flows and stronger growth requirements, conditions that can distribute control across multiple modules and allow partial uncoupling between flow dynamics and specific morphogenetic outputs. This comparison motivates quantitative endpoints in amniotes that go beyond PS length/width to include flow metrics and polarity readouts, enabling more direct cross-clade tests of which aspects of morphogenesis are Wnt/PCP-dependent.

Together, these issues motivate a stage-dependent view of Wnt/PCP function across amniote midline development. PCP perturbation can alter PS geometry without abolishing large-scale flows, suggesting that pathway activity is not equivalent to flow presence. Informative tests should quantify how PCP perturbations affect the symmetry, timing, and reproducibility of flows while monitoring planar polarity and junctional/cytoskeletal readouts in the epiblast. Whether post-PS notochord elongation and node regression are PCP dependent remains unresolved (Zhao et al., 2025). Resolving these links will unify models among vertebrates.

Across vertebrates, the Wnt/PCP pathway is a conserved organizer of planar polarization, however, its developmental roles diverge with embryonic architecture and stage (Figure 1). In non-amniotes, Wnt/PCP-regulated CE provides a relatively direct, largely proliferation-independent route to midline elongation across key gastrulation windows. By contrast, in amniotes, particularly in avians, PS-based gastrulation introduces an early proliferation-sensitive phase in which the Wnt/PCP pathway contributes to streak geometry, while the polonaise movements can still initiate and persist even when PS extension is impaired. In the chick embryo, these flows can also exhibit pre-node LR asymmetry, indicating a detectable laterality bias upstream of a mature organizer-centric gene program. After PS extension, a second phase follows in which axial morphogenesis becomes comparatively mitosis resistant and embryos can scale down while preserving core morphogenetic trajectories. Taken together, these comparisons support a stage-aware framework in which a conserved signaling modules is deployed within clade-specific developmental architectures, producing distinct coupling relationships among signaling, proliferation-dependent tissue growth, tissue-scale flows, and early laterality.