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Molecular architecture underlying fluid absorption by the developing inner ear
Mutations of SLC26A4 are a common cause of hearing loss associated with enlargement of the endolymphatic sac (EES). Slc26a4 expression in the developing mouse endolymphatic sac is required for acquisition of normal inner ear structure and function. Here, we show that the mouse endolymphatic sac abso...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634787/ https://www.ncbi.nlm.nih.gov/pubmed/28994389 http://dx.doi.org/10.7554/eLife.26851 |
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author | Honda, Keiji Kim, Sung Huhn Kelly, Michael C Burns, Joseph C Constance, Laura Li, Xiangming Zhou, Fei Hoa, Michael Kelley, Matthew W Wangemann, Philine Morell, Robert J Griffith, Andrew J |
author_facet | Honda, Keiji Kim, Sung Huhn Kelly, Michael C Burns, Joseph C Constance, Laura Li, Xiangming Zhou, Fei Hoa, Michael Kelley, Matthew W Wangemann, Philine Morell, Robert J Griffith, Andrew J |
author_sort | Honda, Keiji |
collection | PubMed |
description | Mutations of SLC26A4 are a common cause of hearing loss associated with enlargement of the endolymphatic sac (EES). Slc26a4 expression in the developing mouse endolymphatic sac is required for acquisition of normal inner ear structure and function. Here, we show that the mouse endolymphatic sac absorbs fluid in an SLC26A4-dependent fashion. Fluid absorption was sensitive to ouabain and gadolinium but insensitive to benzamil, bafilomycin and S3226. Single-cell RNA-seq analysis of pre- and postnatal endolymphatic sacs demonstrates two types of differentiated cells. Early ribosome-rich cells (RRCs) have a transcriptomic signature suggesting expression and secretion of extracellular proteins, while mature RRCs express genes implicated in innate immunity. The transcriptomic signature of mitochondria-rich cells (MRCs) indicates that they mediate vectorial ion transport. We propose a molecular mechanism for resorption of NaCl by MRCs during development, and conclude that disruption of this mechanism is the root cause of hearing loss associated with EES. |
format | Online Article Text |
id | pubmed-5634787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-56347872017-10-12 Molecular architecture underlying fluid absorption by the developing inner ear Honda, Keiji Kim, Sung Huhn Kelly, Michael C Burns, Joseph C Constance, Laura Li, Xiangming Zhou, Fei Hoa, Michael Kelley, Matthew W Wangemann, Philine Morell, Robert J Griffith, Andrew J eLife Developmental Biology Mutations of SLC26A4 are a common cause of hearing loss associated with enlargement of the endolymphatic sac (EES). Slc26a4 expression in the developing mouse endolymphatic sac is required for acquisition of normal inner ear structure and function. Here, we show that the mouse endolymphatic sac absorbs fluid in an SLC26A4-dependent fashion. Fluid absorption was sensitive to ouabain and gadolinium but insensitive to benzamil, bafilomycin and S3226. Single-cell RNA-seq analysis of pre- and postnatal endolymphatic sacs demonstrates two types of differentiated cells. Early ribosome-rich cells (RRCs) have a transcriptomic signature suggesting expression and secretion of extracellular proteins, while mature RRCs express genes implicated in innate immunity. The transcriptomic signature of mitochondria-rich cells (MRCs) indicates that they mediate vectorial ion transport. We propose a molecular mechanism for resorption of NaCl by MRCs during development, and conclude that disruption of this mechanism is the root cause of hearing loss associated with EES. eLife Sciences Publications, Ltd 2017-10-10 /pmc/articles/PMC5634787/ /pubmed/28994389 http://dx.doi.org/10.7554/eLife.26851 Text en http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Developmental Biology Honda, Keiji Kim, Sung Huhn Kelly, Michael C Burns, Joseph C Constance, Laura Li, Xiangming Zhou, Fei Hoa, Michael Kelley, Matthew W Wangemann, Philine Morell, Robert J Griffith, Andrew J Molecular architecture underlying fluid absorption by the developing inner ear |
title | Molecular architecture underlying fluid absorption by the developing inner ear |
title_full | Molecular architecture underlying fluid absorption by the developing inner ear |
title_fullStr | Molecular architecture underlying fluid absorption by the developing inner ear |
title_full_unstemmed | Molecular architecture underlying fluid absorption by the developing inner ear |
title_short | Molecular architecture underlying fluid absorption by the developing inner ear |
title_sort | molecular architecture underlying fluid absorption by the developing inner ear |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634787/ https://www.ncbi.nlm.nih.gov/pubmed/28994389 http://dx.doi.org/10.7554/eLife.26851 |
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