title: PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium.
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.
authors.affiliation: Department of Cell Biology, P.O. Box 800732, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Lee
authors.forename: Anna
authors.initials: A
authors.lastname: Andreeva
authors.forename: Conor W
authors.initials: CW
authors.lastname: Sipe
authors.forename: Lixia
authors.initials: L
authors.lastname: Liu
authors.forename: Amy
authors.initials: A
authors.lastname: Cheng
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Lu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity; D000072261:Dishevelled Proteins; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D009154:Mutation; D024462:Myosin Type II / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; C000606582:Dvl2 protein, mouse; D051157:Frizzled Receptors; C486339:Fzd3 protein, mouse; D010750:Phosphoproteins; D051153:Wnt Proteins; D016596:Vinculin; C486452:Ptk7 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D024462:Myosin Type II