Cell autonomous polarization by the planar cell polarity signaling pathway

Alexis T. Weiner, Silas Boye Nissen, Kaye Suyama, Bomsoo Cho, Gandhy Pierre-Louis and Jeffrey D. Axelrod ()
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Alexis T. Weiner: Stanford University School of Medicine
Silas Boye Nissen: Stanford University School of Medicine
Kaye Suyama: Stanford University School of Medicine
Bomsoo Cho: Stanford University School of Medicine
Gandhy Pierre-Louis: Stanford University School of Medicine
Jeffrey D. Axelrod: Stanford University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract As epithelial cells polarize in the tissue plane, the Planar Cell Polarity (PCP) signaling module segregates two distinct molecular subcomplexes to opposite sides of cells. Homodimers of the atypical cadherin Flamingo form bridges linking opposite complexes in neighboring cells, coordinating their direction of polarization. Feedback is required for cell polarization, but whether feedback requires intercellular and/or intracellular pathways is unknown. Using novel tools, we show that cells lacking Flamingo, or bearing a homodimerization-deficient Flamingo, polarize autonomously, indicating that functional PCP subcomplexes form and segregate cell-autonomously. Furthermore, we identify feedback pathways and propose an asymmetry amplifying mechanism that operate cell-autonomously. The intrinsic logic of PCP signaling is therefore more similar to that in single cell systems than was previously recognized.

Date: 2025
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DOI: 10.1038/s41467-025-64563-z

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