The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear

The vestibular maculae of the inner ear contain sensory receptor hair cells that detect linear acceleration, contribute to equilibrioception, and thereby coordinate posture and ambulatory movements. These hair cells are divided between two groups, separated by a line of polarity reversal (LPR), with oppositely oriented planar-polarized stereociliary bundles that detect motion in opposite directions. The transcription factor EMX2 is known to establish this planar polarized organization by regulating the distribution of the transmembrane receptor GPR156 at the hair cell surface in one group of cells, however those genes regulated by EMX2 in this context were previously not known. We have identified the serine threonine kinase STK32A as a downstream effector negatively regulated by EMX2. Stk32a is expressed in hair cells on one side of the LPR in a pattern complementary to Emx2 due to transcriptional repression. Stk32a is necessary to align the intrinsic polarity of the bundle with the core planar cell polarity (PCP) proteins in EMX2-negative regions, and is sufficient to reorient bundles when ectopically expressed in neighboring EMX2-positive regions. We demonstrate that STK32a reinforces LPR formation by regulating the apical localization of GPR156. These observations support a model in which bundle orientation is determined through separate mechanisms in hair cells on opposite sides of the LPR, with EMX2-mediated repression of Stk32a determining the position of the LPR. HighlightsO_LISTK32A is a planar polarity effector that is negatively regulated by the transcription factor EMX2 C_LIO_LIStk32a is necessary and sufficient to determine vestibular hair cell stereociliary bundle orientation C_LIO_LISTK32A contributes to the post-translational regulation of GPR156, preventing GPR156 localization in the absence of EMX2 C_LI