Elvis Huarcaya Najarro


The white arrows indicate the direction of the hair bundle. Wntless hair bundles point in various directions compared with the wild type controls.

Planar cell polarity (PCP) proteins localize asymmetrically to instruct cell polarity within the tissue plane, with defects leading to deformities of the limbs, neural tube, and inner ear. Wnt proteins are evolutionarily conserved polarity cues, yet Wnt mutants display variable PCP defects, thus how Wnts regulate PCP remains unresolved. Here, we used the developing cochlea as a model system to show that secreted Wnts regulate PCP through polarizing a specific subset of PCP proteins. Conditional deletion of Wntless or Porcupine, both essential for secretion of Wnts, caused misrotated sensory cells and shortened cochlea-both hallmarks of PCP defects. Wntless-deficient cochleae lacked the polarized PCP components Dishevelled1/2 and Frizzled3/6, while other PCP proteins (Vangl1/2, Celsr1, Dishevelled3) remained localized. We identified seven Wnt paralogues, including the major PCP regulator Wnt5a, which was surprisingly dispensable for planar polarization in the cochlea. Finally, Vangl2 haploinsufficiency markedly accentuated sensory cell polarization defects in Wntless-deficient cochlea. Together our study unmasked a dual regulation of planar polarization by secreted Wnts and Vangl2 to ensure proper tissue development.

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