Epithelial supporting cells can differentiate into outer hair cells and Deiters' cells in the cultured organ of Corti

2002 ◽  
Vol 59 (10) ◽  
pp. 1744-1757 ◽  
Author(s):  
B. Malgrange ◽  
M. Thiry ◽  
T. R. Van de Water ◽  
L. Nguyen ◽  
G. Moonen ◽  
...  
eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Sung-Ho Huh ◽  
Mark E Warchol ◽  
David M Ornitz

The sensory and supporting cells (SCs) of the organ of Corti are derived from a limited number of progenitors. The mechanisms that regulate the number of sensory progenitors are not known. Here, we show that Fibroblast Growth Factors (FGF) 9 and 20, which are expressed in the non-sensory (Fgf9) and sensory (Fgf20) epithelium during otic development, regulate the number of cochlear progenitors. We further demonstrate that Fgf receptor (Fgfr) 1 signaling within the developing sensory epithelium is required for the differentiation of outer hair cells and SCs, while mesenchymal FGFRs regulate the size of the sensory progenitor population and the overall cochlear length. In addition, ectopic FGFR activation in mesenchyme was sufficient to increase sensory progenitor proliferation and cochlear length. These data define a feedback mechanism, originating from epithelial FGF ligands and mediated through periotic mesenchyme that controls the number of sensory progenitors and the length of the cochlea.


2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Paola Perin ◽  
Simona Tritto ◽  
Laura Botta ◽  
Jacopo Maria Fontana ◽  
Giulia Gastaldi ◽  
...  

We characterize the expression pattern of aquaporin-6 in the mouse inner ear by RT-PCR and immunohistochemistry. Our data show that in the inner ear aquaporin-6 is expressed, in both vestibular and acoustic sensory epithelia, by the supporting cells directly contacting hair cells. In particular, in the Organ of Corti, expression was strongest in Deiters' cells, which provide both a mechanical link between outer hair cells (OHCs) and the Organ of Corti, and an entry point for ion recycle pathways. Since aquaporin-6 is permeable to both water and anions, these results suggest its possible involvement in regulating OHC motility, directly through modulation of water and chloride flow or by changing mechanical compliance in Deiters' cells. In further support of this role, treating mice with salicylates, which impair OHC electromotility, dramatically reduced aquaporin-6 expression in the inner ear epithelia but not in control tissues, suggesting a role for this protein in modulating OHCs' responses.


Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1041-1053 ◽  
Author(s):  
M.W. Kelley ◽  
X.M. Xu ◽  
M.A. Wagner ◽  
M.E. Warchol ◽  
J.T. Corwin

The mammalian organ of Corti has one of the most highly ordered patterns of cells in any vertebrate sensory epithelium. A single row of inner hair cells and three or four rows of outer hair cells extend along its length. The factors that regulate the formation of this strict pattern are unknown. In order to determine whether retinoic acid plays a role during the development of the organ of Corti, exogenous retinoic acid was added to embryonic mouse cochleae in vitro. Exogenous retinoic acid significantly increased the number of cells that developed as hair cells and resulted in large regions of supernumerary hair cells and supporting cells containing two rows of inner hair cells and up to 11 rows of outer hair cells. The effects of retinoic acid were dependent on concentration and on the timing of its addition. Western blot analysis indicated that cellular retinoic acid binding protein (CRABP) was present in the sensory epithelium of the embryonic cochlea. The amount of CRABP apparently increased between embryonic day 14 and postnatal day 1, but CRABP was not detectable in sensory epithelia from adults. A retinoic acid reporter cell line was used to demonstrate that retinoic acid was also present in the developing organ of Corti between embryonic day 14 and postnatal day 1, and was also present in adult cochleae at least in the vicinity of the modiolus. These results suggest that retinoic acid is involved in the normal development of the organ of Corti and that the effect of retinoic acid may be to induce a population of prosensory cells to become competent to differentiate as hair cells and supporting cells.


2019 ◽  
Vol 116 (42) ◽  
pp. 21054-21060 ◽  
Author(s):  
Lina Jansson ◽  
Michael Ebeid ◽  
Jessica W. Shen ◽  
Tara E. Mokhtari ◽  
Lee A. Quiruz ◽  
...  

Development of multicellular organs requires the coordination of cell differentiation and patterning. Critical for sound detection, the mammalian organ of Corti contains functional units arranged tonotopically along the cochlear turns. Each unit consists of sensory hair cells intercalated by nonsensory supporting cells, both specified and radially patterned with exquisite precision during embryonic development. However, how cell identity and radial patterning are jointly controlled is poorly understood. Here we show that β-catenin is required for specification of hair cell and supporting cell subtypes and radial patterning of the cochlea in vivo. In 2 mouse models of conditional β-catenin deletion, early specification of Myosin7-expressing hair cells and Prox1-positive supporting cells was preserved. While β-catenin-deficient cochleae expressed FGF8 and FGFR3, both of which are essential for pillar cell specification, the radial patterning of organ of Corti was disrupted, revealed by aberrant expression of cadherins and the pillar cell markers P75 and Lgr6. Moreover, β-catenin ablation caused duplication of FGF8-positive inner hair cells and reduction of outer hair cells without affecting the overall hair cell density. In contrast, in another transgenic model with suppressed transcriptional activity of β-catenin but preserved cell adhesion function, both specification and radial patterning of the organ of Corti were intact. Our study reveals specific functions of β-catenin in governing cell identity and patterning mediated through cell adhesion in the developing cochlea.


2020 ◽  
Author(s):  
Victoria Lukashkina ◽  
Snezana Levic ◽  
Patricio Simões ◽  
Zhenhang Xu ◽  
Joseph DiGuiseppi ◽  
...  

Abstract We used optogenetics to investigate the control of auditory sensitivity by cochlear supporting cells that scaffold outer hair cells, which transduce and amplify cochlear responses to sound. In vivo and in vitro measurements of sound-induced cochlear mechanical and electrical responses were made from mice that conditionally expressed nonselective cationic channelrhodopsins in Deiters’ and outer pillar supporting cells in the organ of Corti. We demonstrated that cochlear light-stimulation and subsequent activation of channelrhodopsins depolarized the supporting cells, changed their extracellular electrical environment, and sensitized insensitive and desensitized sensitive cochlear responses to sound. We concluded that outer hair cells, Deiters’ cells and outer pillar cells interact through feedback which regulates their immediate ionic and electrical environment and controls energy flow in the mammalian cochlea to optimize its performance over its entire dynamic range. Activation of the supporting cell channelrhodopsins shunts this feedback system and restores cochlear sensitivity to a set level.


1999 ◽  
Vol 27 (2) ◽  
pp. 73-77 ◽  
Author(s):  
Miguel A. Lopez-Gonzalez ◽  
Juan M. Guerrero ◽  
Francisco Rojas ◽  
Carmen Osuna ◽  
Francisco Delgado

ORL ◽  
1988 ◽  
Vol 50 (6) ◽  
pp. 363-370 ◽  
Author(s):  
Joseph B. Nadol, Jr.

1981 ◽  
Vol 89 (4) ◽  
pp. 638-645 ◽  
Author(s):  
Scott A. Estrem ◽  
Richard W. Babin ◽  
Jai H. Ryu ◽  
Kenneth C. Moore

Cochleas from 12 guinea pigs were evaluated using light, scanning, and transmission electron microscopy after systemic administration of cis-diamminedichloroplatinum (cis-DDP). Administration of cis-DDP resulted in loss of the Preyer reflex and degeneration of outer hair cells (OHC) with increased dose. The OHC degeneration was most pronounced in the basal turns of the cochlea with greatest severity in the inner row. Ultrastructural evidence of OHC degeneration included dilatation of the parietal membranes, softening of the cuticular plate, increased vacuolization and increased numbers of lysosome-like bodies in the apical portion of the cell. Supporting cells appeared more sensitive than OHC. Alteration of supporting cell ultrastructure preceded detectable change in OHC. Injury to the supporting cells was noted with intracellular vesiculation and increased autophagocytosis.


1978 ◽  
Vol 26 (4) ◽  
pp. 313-317 ◽  
Author(s):  
T Omata ◽  
I Ohtani ◽  
K Ohtsuki ◽  
J Ouchi

A method for the detection of lactic dehydrogenase enzymatic activity in outer hair cells of the rabbit is described. The membranous labyrinth with temporal bone was prefixed in glutaraldehyde. After being placed into the incubation medium, it was postfixed in osmium tetroxide. Specimens of the organ of Corti were removed. Then the specimens were embedded in water-soluble glycol and cut with a cryostat for light microscopy, and also they were embedded in Epon and cut for light and electron microscopy. Sectioning of the membranous labyrinth was very easily made when the specimens were embedded in both the water-soluble glycol and the Epon. The structures of the frozen sections as well as the Epon-embedded ones were well preserved. In the frozen sections the preservation and localization of reaction products were thoroughly kept, but monoformazan of the Epon-embedded sections was soluble.


Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1581-1590 ◽  
Author(s):  
P. Chen ◽  
N. Segil

Strict control of cellular proliferation is required to shape the complex structures of the developing embryo. The organ of Corti, the auditory neuroepithelium of the inner ear in mammals, consists of two types of terminally differentiated mechanosensory hair cells and at least four types of supporting cells arrayed precisely along the length of the spiral cochlea. In mice, the progenitors of greater than 80% of both hair cells and supporting cells undergo their terminal division between embryonic day 13 (E13) and E14. As in humans, these cells persist in a non-proliferative state throughout the adult life of the animal. Here we report that the correct timing of cell cycle withdrawal in the developing organ of Corti requires p27(Kip1), a cyclin-dependent kinase inhibitor that functions as an inhibitor of cell cycle progression. p27(Kip1) expression is induced in the primordial organ of Corti between E12 and E14, correlating with the cessation of cell division of the progenitors of the hair cells and supporting cells. In wild-type animals, p27(Kip1) expression is downregulated during subsequent hair cell differentiation, but it persists at high levels in differentiated supporting cells of the mature organ of Corti. In mice with a targeted deletion of the p27(Kip1) gene, proliferation of the sensory cell progenitors continues after E14, leading to the appearance of supernumerary hair cells and supporting cells. In the absence of p27(Kip1), mitotically active cells are still observed in the organ of Corti of postnatal day 6 animals, suggesting that the persistence of p27(Kip1) expression in mature supporting cells may contribute to the maintenance of quiescence in this tissue and, possibly, to its inability to regenerate. Homozygous mutant mice are severely hearing impaired. Thus, p27(Kip1) provides a link between developmental control of cell proliferation and the morphological development of the inner ear.


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