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Peer-reviewedCC BY-NC-NDNature communications

Epithelial-mesenchymal Wnt crosstalk directs planar cell polarity in the developing cochlea.

  • Ippei Kishimoto1
  • Abel P David2,3
  • Kevin P Rose4
  • Balasubramanian Narasimhan5
  • Bradley Efron5
  • Sara E Billings1
  • Erin L Su1
  • Wuxing Dong1
  • Taha A Jan6
  • Ronna Hertzano4
  • Alan G Cheng7
7 affiliations
  1. 1Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  2. 2Department of Otolaryngology-Head & Neck Surgery, Northwestern Medicine, Chicago, IL, USA.
  3. 3Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  4. 4Section on Omics and Translational Science of Hearing, Neurotology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
  5. 5Department of Statistics, Stanford University, Stanford, CA, USA.
  6. 6Department of Otolaryngology - Head and Neck Surgery, Epithelial Biology Center, Vanderbilt Center for Stem Cell Biology, Center for Computational Systems Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
  7. 7Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
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Abstract

Cochlear hair cells are precisely oriented by planar cell polarity. Wnt proteins direct planar cell polarity in vertebrates, but their roles in regulating cochlear planar cell polarity remain unclear. Here, we inhibit Wnt secretion by ablating epithelial Wntless and find shortened cochlea, mild hair cell misorientation and mislocalization of core planar cell polarity proteins, Fzd6 and Dvl2. Computational analysis predicts that epithelial Wnts (Wnt5a, Wnt7a, Wnt7b) and Wnt5a from surrounding periotic mesenchyme act on developing hair cells. Deletion of epithelial Wnt5a, Wnt7a, and Wnt7b additively shortens the cochlea without causing hair cell misorientation or Fzd6/Dvl2 mislocalization. Moreover, deletion of epithelial or both epithelial and mesenchymal Wnt5a fails to cause polarity defects. However, ablating both epithelial and mesenchymal Wntless severely shortens the cochlea and causes hair cell misorientation and mislocalized core planar cell polarity proteins. Thus, Wnts serve as global instructive cues directing cochlear outgrowth and hair cell polarization, with remarkable redundancy of distinct Wnts across epithelial and mesenchymal compartments to ensure a fail-safe developmental program.

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Cite

BibTeXRIS
BibTeX
@article{kishimoto2026epithelialmesenchymal,
  title = {{Epithelial-mesenchymal Wnt crosstalk directs planar cell polarity in the developing cochlea.}},
  author = {Ippei Kishimoto and Abel P David and Kevin P Rose and Balasubramanian Narasimhan and Bradley Efron and Sara E Billings and Erin L Su and Wuxing Dong and Taha A Jan and Ronna Hertzano and Alan G Cheng},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77522-z},
  url = {https://europepmc.org/article/MED/42881149},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Epithelial-mesenchymal Wnt crosstalk directs planar cell polarity in the developing cochlea.
AU  - Ippei Kishimoto
AU  - Abel P David
AU  - Kevin P Rose
AU  - Balasubramanian Narasimhan
AU  - Bradley Efron
AU  - Sara E Billings
AU  - Erin L Su
AU  - Wuxing Dong
AU  - Taha A Jan
AU  - Ronna Hertzano
AU  - Alan G Cheng
PY  - 2026
DA  - 2026/09/16
JO  - Nature communications
DO  - 10.1038/s41467-026-77522-z
UR  - https://europepmc.org/article/MED/42881149
AB  - Cochlear hair cells are precisely oriented by planar cell polarity. Wnt proteins direct planar cell polarity in vertebrates, but their roles in regulating cochlear planar cell polarity remain unclear. Here, we inhibit Wnt secretion by ablating epithelial Wntless and find shortened cochlea, mild hair cell misorientation and mislocalization of core planar cell polarity proteins, Fzd6 and Dvl2. Computational analysis predicts that epithelial Wnts (Wnt5a, Wnt7a, Wnt7b) and Wnt5a from surrounding periotic mesenchyme act on developing hair cells. Deletion of epithelial Wnt5a, Wnt7a, and Wnt7b additively shortens the cochlea without causing hair cell misorientation or Fzd6/Dvl2 mislocalization. Moreover, deletion of epithelial or both epithelial and mesenchymal Wnt5a fails to cause polarity defects. However, ablating both epithelial and mesenchymal Wntless severely shortens the cochlea and causes hair cell misorientation and mislocalized core planar cell polarity proteins. Thus, Wnts serve as global instructive cues directing cochlear outgrowth and hair cell polarization, with remarkable redundancy of distinct Wnts across epithelial and mesenchymal compartments to ensure a fail-safe developmental program.
SN  - 2041-1723
ER  -