Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea.
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.
Dabdoub
Alain
A
Section on Developmental Neuroscience, NIDCD, National Institutes of Health, Rockville, MD 20850, USA. dabdouba@nidcd.nih.gov
Donohue
Maura J
MJ
Brennan
Angela
A
Wolf
Vladimir
V
Montcouquiol
Mireille
M
Sassoon
David A
DA
Hseih
Jen-Chih
JC
Rubin
Jeffrey S
JS
Salinas
Patricia C
PC
Kelley
Matthew W
MW
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
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