A molecular blueprint at the apical surface establishes planar asymmetry in cochlear hair cells

Abstract

Sound perception relies on the planar polarization of the mechanosensory hair cell apex, which develops a V-shaped stereocilia bundle pointing toward an eccentric kinocilium. It remains unknown how intrinsically asymmetric bundles arise and are concomitantly oriented in the tissue. We report here that mInsc, LGN, and Gαi proteins, which classically regulate mitotic spindle orientation, are polarized in a lateral microvilli-free region, or "bare zone," at the apical hair cell surface. By creating and extending the bare zone, these proteins trigger a relocalization of the eccentric kinocilium midway toward the cell center. aPKC is restrained medially by mInsc/LGN/Gαi, resulting in compartmentalization of the apical surface that imparts the V-shaped distribution of stereocilia and brings the asymmetric bundle in register with the relocalized kinocilium. Gαi is additionally required for lateral orientation of cochlear hair cells, providing a possible mechanism to couple the emergence of asymmetric stereocilia bundles with planar cell polarity.