JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
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Domineering non-autonomy in Vangl1;Vangl2 double mutants demonstrates intercellular PCP signaling in the vertebrate inner ear.

The organization of polarized stereociliary bundles is critical for the function of the inner ear sensory receptor hair cells that detect sound and motion, and these cells present a striking example of Planar Cell Polarity (PCP); the coordinated orientation of polarized structures within the plane of an epithelium. PCP is best understood in Drosophila where the essential genes regulating PCP were first discovered, and functions for the core PCP proteins encoded by these genes have been deciphered through phenotypic analysis of core PCP gene mutants. One illuminating phenotype is the domineering non-autonomy that is observed where abrupt disruptions in PCP signaling impacts the orientation of neighboring wild type cells, because this demonstrates local intercellular signaling mediated by the core PCP proteins. Using Emx2-Cre to generate an analogous mutant boundary in the mouse inner ear, we disrupted vertebrate PCP signaling in Vangl1;Vangl2 conditional knockouts. Due to unique aspects of vestibular anatomy, core PCP protein distribution along the mutant boundary generated in the utricle resembles the proximal side of vang mutant clones in the Drosophila wing, while the boundary in the saccule resembles and the distal side. Consistent with these protein distributions, a domineering non-autonomy phenotype occurs along the Emx2-Cre boundary in the mutant utricle that does not occur in the saccule. These results further support the hypothesis that core PCP function is conserved in vertebrates by demonstrating intercellular PCP signaling in the sensory epithelia of the mouse ear.

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