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

ABSTRACT: 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.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.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.

SUBMITTER: Lee J

PROVIDER: S-EPMC3407606 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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

Lee Jianyi J Andreeva Anna A Sipe Conor W CW Liu Lixia L Cheng Amy A Lu Xiaowei X

Current biology : CB 20120503 11

<h4>Background</h4>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.<h4>Results</h4>Here we show that, in the mammalian auditory epithelium, Ptk7 is not required for membrane re ...[more]

PMID: 22560610

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Project description:Vestibular organs have unique planar cell polarity (Figure 1A), and their normal development and function are dependent on the regular polarity of cilia (Figure 1B) requires. Rab11a is a small G protein that participates in the transportation of intracellular and extracellular materials required for polarity formation; however, our understanding of the mechanisms of the actions of Rab11a in vestibular organs is limited. Here, we showed that the general shape of the utricle was abnormal in Rab11a CKO/CKO mice. These mice also showed abnormal morphology of the stereocilia bundles, which were reduced in both length and number, as well as disturbed tissue-level polarity. Rab11a affected the distribution of polarity proteins in the vestibular organs, indicating that the normal development of cilia requires Rab11a and intraflagellar transportation. Furthermore, small G protein migration works together with intraflagellar transportation in the normal development of cilia. FIGURE 1Morphological changes of stereocilia in the extrastriolar hair cells from Rab11a single or Rab11a/IFT88 double-mutant utricles. (A) Medial view of a mouse left inner ear with its five vestibular sensory organs (gray). Enlarged are the utricle showing their subdivisions, LPR (yellow line), and striola (blue). LES, lateral extrastriola; MES, medial extrastriola; LPR, line of polarity reversal. (B) Schematic view of vestibular hair cell. Kinocilium is marked with ace-tubulin. Basal body is marked with γ-tubulin. (C,C1,D,D1) Normal appearance of the stereocilia of extrastriolar hair cells of wild-type controls. (E,E1,F,F1) Altered morphology in Rab11a CKO/CKO animals. (G,G1,H,H1) The changes in the stereocilia morphology were more severe in Rab11a CKO/CKO /IFT 88 CKO/+ mice. (I-L) Higher magnification of confocal images of hair cells. (M-P) Scanning electron microscopy images of hair cells from wild-type controls and Rab11a mutants. (I,M) Morphology of normal. hair cells of wild-type controls. (J,N) The number of stereocilia on a single hair cell was deceased in the Rab11a mutant. (K,O) Stereocilia were shorter in mutants compared to the wild-type controls. (L,P) The staircase-like hair bundle architecture of hair cells was lost in Rab11a mutant mice. (Q) The percentage of hair cells with abnormal development of static cilia bundles in the extrastriola region was counted as a percentage of the total (n = 5). The percentage of abnormal hair cells was higher in Rab11a CKO/CKO , IFT88 CKO/+ mice compared to Rab11a CKO/CKO . The abnormal ratios of single and double knockout hair cells were 42.1 ± 5.7 and 71.5 ± 10.4, respectively. In (A-J), for all primary panels, hair cell stereociliary bundles were marked with phalloidin (green), the actin-rich cuticular plate of hair cells was labeled with β-spectrin (red), while the basal body of the hair cell was labeled with γ-tubulin (blue). Scale bars: 10 μm (C-H1), 5 μm (J-N). *P < 0.05.

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

Publications

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

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