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Elife. 2017 Oct 10;6. pii: e26851. doi: 10.7554/eLife.26851.

Molecular architecture underlying fluid absorption by the developing inner ear.

Author information

1
Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States.
2
Anatomy and Physiology Department, Kansas State University, Manhattan, United States.
3
Developmental Neuroscience Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States.
4
Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States.
5
Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States.

Abstract

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.

KEYWORDS:

RNA-seq; Slc26a4; developmental biology; endolymphatic sac; gene array; mouse; neuroscience; organ culture; stem cells

PMID:
28994389
PMCID:
PMC5634787
DOI:
10.7554/eLife.26851
[Indexed for MEDLINE]
Free PMC Article

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