A Molecular Blueprint at the Apical Surface Establishes Planar Asymmetry in Cochlear Hair Cells

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 G alpha i 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/G alpha i, 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. G alpha i 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.