Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2

Abstract A conserved line of polarity reversal (LPR) demarcates hair cells into two regions of opposite orientation in the otolith organs of the inner ear. The functional significance of this arrangement is not known. Using gene knockout and conditional knockouts (cKO) mice, we show that the Emx2 encoded transcription factor establishes the LPR and bidirectional sensitivity of the otolith organ by mediating hair bundle orientation in HCs and neuronal selectivity in HCs and supporting cells. In addition to Emx2 cKO, we generated another mouse strain without bidirectional sensitivity in otolith organs, Tmie cKO, in which HCs within the Emx2 expression domain lack mechanotransduction and thus are rendered non-functional. Behavioral analyses of both Emx2 cKO and Tmie cKO mice indicate that the LPR is specifically required for mice to swim comfortably and to traverse a balance beam efficiently, but LPR is not required for mice to stay on a rotating rod.