PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium

Jianyi Lee, Anna Andreeva, Conor W. Sipe, Lixia Liu, Amy Cheng, Xiaowei Lu

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: Planar cell polarity (PCP) signaling is a key regulator of epithelial morphogenesis, including neural tube closure and the orientation of inner ear sensory hair cells, and is mediated by a conserved noncanonical Wnt pathway. Ptk7 is a novel vertebrate-specific regulator of PCP, yet the mechanisms by which Ptk7 regulates mammalian epithelial PCP remain poorly understood. Results: Here we show that, in the mammalian auditory epithelium, Ptk7 is not required for membrane recruitment of Dishevelled 2; Ptk7 and Frizzled3/Frizzled6 receptors act in parallel and have opposing effects on hair cell PCP. Mosaic analysis identified a requirement of Ptk7 in neighboring supporting cells for hair cell PCP. Ptk7 and the noncanonical Wnt pathway differentially regulate a contractile myosin II network near the apical surface of supporting cells. We provide evidence that this apical myosin II network exerts polarized contractile tension on hair cells to align their PCP, as revealed by asymmetric junctional recruitment of vinculin, a tension-sensitive actin binding protein. In Ptk7 mutants, compromised myosin II activity resulted in loss of planar asymmetry and reduced junctional localization of vinculin. By contrast, vinculin planar asymmetry and stereociliary bundle orientation were restored in Fz3 -/-;Ptk7 -/- double mutants. Conclusions: These findings suggest that PTK7 acts in conjunction with the noncanonical Wnt pathway to orient epithelial PCP through modulation of myosin II-based contractile tension between supporting cells and hair cells.

Original languageEnglish
Pages (from-to)956-966
Number of pages11
JournalCurrent Biology
Volume22
Issue number11
DOIs
Publication statusPublished - Jun 5 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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