TY - JOUR TI - Molecular architecture underlying fluid absorption by the developing inner ear AU - Honda, Keiji AU - Kim, Sung Huhn AU - Kelly, Michael C AU - Burns, Joseph C AU - Constance, Laura AU - Li, Xiangming AU - Zhou, Fei AU - Hoa, Michael AU - Kelley, Matthew W AU - Wangemann, Philine AU - Morell, Robert J AU - Griffith, Andrew J A2 - Nathans, Jeremy VL - 6 PY - 2017 DA - 2017/10/10 SP - e26851 C1 - eLife 2017;6:e26851 DO - 10.7554/eLife.26851 UR - https://doi.org/10.7554/eLife.26851 AB - 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. KW - endolymphatic sac KW - Slc26a4 KW - organ culture KW - RNA-seq KW - gene array JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -