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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
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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. |
format | Online Article Text |
id | pubmed-10202454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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