TY - JOUR
T1 - PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium
AU - Lee, Jianyi
AU - Andreeva, Anna
AU - Sipe, Conor W.
AU - Liu, Lixia
AU - Cheng, Amy
AU - Lu, Xiaowei
N1 - Funding Information:
We thank Paul Adler, Douglas DeSimone, Alan “Rick” Horwitz, Raymond Keller, Martin Schwartz, Ann Sutherland, and members of the X.L. laboratory for helpful comments on the manuscript; Robert Adelstein and Matthew Kelley for Myh10 DN mice; and Jeremy Nathans and Yanshu Wang for Fz plasmids, antibodies, and mice. This study was supported by a Basil O'Connor Starter Scholar Research Awards (#5-FY07-166) from the March of Dimes Foundation and the NIH grant R01 DC009238 (to X.L.). C.W.S. was supported by NIH training grant T32 GM008136 for Cell and Molecular Biology at the University of Virginia.
PY - 2012/6/5
Y1 - 2012/6/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cub.2012.03.068
DO - 10.1016/j.cub.2012.03.068
M3 - Article
C2 - 22560610
AN - SCOPUS:84861839886
VL - 22
SP - 956
EP - 966
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 11
ER -