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Peer-reviewedCC BY-NCScience Advances

Dishevelled-mediated clustering stabilizes Frizzled6 and Vangl2 to establish planar cell polarity in the mammalian skin

  1. 1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

Abstract

Planar cell polarity (PCP) in epithelia is characterized by the polarized distribution of two opposing, membrane-associated PCP complexes across cell junctions. Transmembrane components of the PCP complex bridge cell junctions and organize into punctate, intercellular assemblies that exhibit a high degree of stability. Here, we define the contributions of the cytoplasmic PCP protein, Dishevelled (Dvl), in the sub-micron scale organization and stability of PCP complexes. Using endogenously-tagged fluorescent PCP reporters in the embryonic mouse epidermis, we quantify PCP protein mobility and clustering during polarization. We find that as transmembrane proteins immobilize into puncta, Dishevelled (Dvl2/3) co-accumulates with its transmembrane partner Frizzled (Fz6) in a polarized manner and stabilizes clusters of PCP complexes. We identify a previously unknown function for the oligomerizing DIX domain of Dvl3, typically associated with Wnt signaling, in Dvl3 asymmetric localization. These observations underscore a role for Dvl oligomerization in assembly and stabilization of asymmetric PCP puncta.

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BibTeX
@article{sil2026dishevelledmediated,
  title = {{Dishevelled-mediated clustering stabilizes Frizzled6 and Vangl2 to establish planar cell polarity in the mammalian skin}},
  author = {Parijat Sil and Brandon Trejo and Katherine A. Little and Danelle Devenport},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeh6920},
  url = {https://www.science.org/doi/10.1126/sciadv.aeh6920},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Dishevelled-mediated clustering stabilizes Frizzled6 and Vangl2 to establish planar cell polarity in the mammalian skin
AU  - Parijat Sil
AU  - Brandon Trejo
AU  - Katherine A. Little
AU  - Danelle Devenport
PY  - 2026
DA  - 2026/10/09
JO  - Science Advances
DO  - 10.1126/sciadv.aeh6920
UR  - https://www.science.org/doi/10.1126/sciadv.aeh6920
AB  - Planar cell polarity (PCP) in epithelia is characterized by the polarized distribution of two opposing, membrane-associated PCP complexes across cell junctions. Transmembrane components of the PCP complex bridge cell junctions and organize into punctate, intercellular assemblies that exhibit a high degree of stability. Here, we define the contributions of the cytoplasmic PCP protein, Dishevelled (Dvl), in the sub-micron scale organization and stability of PCP complexes. Using endogenously-tagged fluorescent PCP reporters in the embryonic mouse epidermis, we quantify PCP protein mobility and clustering during polarization. We find that as transmembrane proteins immobilize into puncta, Dishevelled (Dvl2/3) co-accumulates with its transmembrane partner Frizzled (Fz6) in a polarized manner and stabilizes clusters of PCP complexes. We identify a previously unknown function for the oligomerizing DIX domain of Dvl3, typically associated with Wnt signaling, in Dvl3 asymmetric localization. These observations underscore a role for Dvl oligomerization in assembly and stabilization of asymmetric PCP puncta.
SN  - 2375-2548
ER  -