title: Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea.
abstract: In the mammalian cochlea, stereociliary bundles located on mechanosensory hair cells within the sensory epithelium are unidirectionally oriented. Development of this planar polarity is necessary for normal hearing as stereociliary bundles are only sensitive to vibrations in a single plane; however, the mechanisms governing their orientation are unknown. We report that Wnt signaling regulates the development of unidirectional stereociliary bundle orientation. In vitro application of Wnt7a protein or inhibitors of Wnt signaling, secreted Frizzled-related protein 1 or Wnt inhibitory factor 1, disrupts bundle orientation. Moreover, Wnt7a is expressed in a pattern consistent with a role in the polarization of the developing stereociliary bundles. We propose that Wnt signaling across the region of developing outer hair cells gives rise to planar polarity in the mammalian cochlea.
authors.affiliation: Section on Developmental Neuroscience, NIDCD, National Institutes of Health, Rockville, MD 20850, USA. dabdouba@nidcd.nih.gov
authors.forename: Alain
authors.initials: A
authors.lastname: Dabdoub
authors.forename: Maura J
authors.initials: MJ
authors.lastname: Donohue
authors.forename: Angela
authors.initials: A
authors.lastname: Brennan
authors.forename: Vladimir
authors.initials: V
authors.lastname: Wolf
authors.forename: Mireille
authors.initials: M
authors.lastname: Montcouquiol
authors.forename: David A
authors.initials: DA
authors.lastname: Sassoon
authors.forename: Jen-Chih
authors.initials: JC
authors.lastname: Hseih
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Rubin
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Salinas
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kelley
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019521:Body Patterning; D002352:Carrier Proteins / Q000494:pharmacology; D016326:Extracellular Matrix Proteins; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000494:pharmacology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000254:growth & development*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012097:Repressor Proteins; D015398:Signal Transduction; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099274:Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099274:Frizzled-Related Proteins; C485569:WIF1 protein, human; C118544:Wif1 protein, mouse; C490508:Wnt7a protein, mouse; C490603:Wnt8b protein, mouse