The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear
- University of Utah, United States
- Boston Children's Hospital, United States
- Jackson Laboratory, United States
Abstract
The vestibular maculae of the inner ear contain sensory receptor hair cells that detect linear acceleration and contribute to equilibrioception to 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 in mouse by regulating the distribution of the transmembrane receptor GPR156 at hair cell boundaries in one group of cells. However, the genes regulated by EMX2 in this context were previously not known. Using mouse as a model, 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 expression in hair cells on the opposite side. 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 maculae, with EMX2-mediated repression of Stk32a determining the final position of the LPR.
Data availability
Sequencing data have been deposited in GEO under accession code GSE218746
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Emx2 KO RNAseqNCBI Gene Expression Omnibus, GSE218746.
Article and author information
Author details
Funding
National Institutes of Health (R01DC013066)
- Michael R Deans
National Institutes of Health (R01DC015242)
- Basile Tarchini
National Institutes of Health (R01DC018304)
- Basile Tarchini
National Institutes of Health (T32HD007491)
- Evan M Ratzan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal work was reviewed for compliance and approved by the Animal Care and Use Committee of The University of Utah (IACUC protocol #00001498) and the Animal Care and Use Committees of The Jackson Laboratory (Animal Use Summary AUS no. 14012)
Copyright
© 2023, Jia et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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