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

  1. Shihai Jia
  2. Evan M Ratzan
  3. Ellison J Goodrich
  4. Raisa Abrar
  5. Luke Heiland
  6. Basile Tarchini
  7. Michael R Deans  Is a corresponding author
  1. University of Utah, United States
  2. Boston Children's Hospital, United States
  3. 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

The following data sets were generated

Article and author information

Author details

  1. Shihai Jia

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1144-4291
  2. Evan M Ratzan

    Interdepartmental Program in Neuroscience, Boston Children's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ellison J Goodrich

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Raisa Abrar

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Luke Heiland

    Department of Otolaryngology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Basile Tarchini

    Jackson Laboratory, Bar Harbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2708-6273
  7. Michael R Deans

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    For correspondence
    michael.deans@utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6319-7945

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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  1. Shihai Jia
  2. Evan M Ratzan
  3. Ellison J Goodrich
  4. Raisa Abrar
  5. Luke Heiland
  6. Basile Tarchini
  7. Michael R Deans
(2023)
The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear
eLife 12:e84910.
https://doi.org/10.7554/eLife.84910

Share this article

https://doi.org/10.7554/eLife.84910

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