Dual regulation of planar polarization by secreted Wnts and Vangl2 in the developing mouse cochlea.
Dual regulation of planar polarization by secreted Wnts and Vangl2 in the developing mouse cochlea.
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DOI：
10.1242/dev.191981
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发表时间：
2020-01-01
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影响因子：
--
通讯作者：
Cheng, Alan G
中科院分区：
文献类型：
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作者：
Huarcaya Najarro, Elvis;Huang, Jennifer;Cheng, Alan G
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 indicates that secreted Wnts and Vangl2 coordinate to ensure proper tissue polarization during development.
