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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 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 opposi...

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Autores principales: Jia, Shihai, Ratzan, Evan M, Goodrich, Ellison J, Abrar, Raisa, Heiland, Luke, Tarchini, Basile, Deans, Michael R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202454/
https://www.ncbi.nlm.nih.gov/pubmed/37144879
http://dx.doi.org/10.7554/eLife.84910
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author Jia, Shihai
Ratzan, Evan M
Goodrich, Ellison J
Abrar, Raisa
Heiland, Luke
Tarchini, Basile
Deans, Michael R
author_facet Jia, Shihai
Ratzan, Evan M
Goodrich, Ellison J
Abrar, Raisa
Heiland, Luke
Tarchini, Basile
Deans, Michael R
author_sort Jia, Shihai
collection PubMed
description 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.
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spelling pubmed-102024542023-05-23 The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear Jia, Shihai Ratzan, Evan M Goodrich, Ellison J Abrar, Raisa Heiland, Luke Tarchini, Basile Deans, Michael R eLife Cell Biology 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. eLife Sciences Publications, Ltd 2023-05-05 /pmc/articles/PMC10202454/ /pubmed/37144879 http://dx.doi.org/10.7554/eLife.84910 Text en © 2023, Jia, Ratzan et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Jia, Shihai
Ratzan, Evan M
Goodrich, Ellison J
Abrar, Raisa
Heiland, Luke
Tarchini, Basile
Deans, Michael R
The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear
title The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear
title_full The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear
title_fullStr The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear
title_full_unstemmed The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear
title_short The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear
title_sort dark kinase stk32a regulates hair cell planar polarity opposite of emx2 in the developing mouse inner ear
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202454/
https://www.ncbi.nlm.nih.gov/pubmed/37144879
http://dx.doi.org/10.7554/eLife.84910
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