scholarly journals The Differentiation of Stem/Progenitor Cells Derived from the Cochlear Sensory Epithelium into Hair Cells Requires a Specific Spatial Supporting Structure of p27kip1-Positive Cells

2020 ◽  
Author(s):  
Xianren Wang ◽  
Xuemei Zhang ◽  
Di Jiang ◽  
Danqing Liu ◽  
Hongyan Jiang
Keyword(s):  
Hair Cell ◽  
Progenitor Cells ◽  
Hair Cells ◽  
Hollow Sphere ◽  
Morphological Changes ◽  
Hollow Spheres ◽  
Solid Sphere ◽  
Sensory Epithelium ◽  
Adherent Culture ◽  
Epithelial Sheets

Abstract Background: Cochlear sensory epithelium-derived progenitor cells initially give rise to compact solid/round spheres. These compact solid/round spheres then gradually convert into irregular and partially hollow spheres, which then ultimately transform into large hollow spheres. The purpose of this study was to observe the differentiation of cochlear sensory epithelium-derived progenitor cells into spheres, and determine factors necessary for their development into hair cells.Methods: Cochlear epithelial sheets from postnatal day 1 C57BL/6 mice were dissociated and sphere cells were cultured. The morphological changes of the spheres were observed, and the different types of sphere cells were examined for their ability to differentiate into hair cell-like cells.Results: Solid spheres formed first, and then gradually transformed into hollow spheres over approximately 260 hours. Adherent culture and Transwell culture assays, and immunohistochemistry staining revealed that neither solid nor hollow sphere cells alone could differentiate into mature hair cells. Solid sphere cells, however, were able to differentiate into mature hair cells when co-cultured with p27kip1-positive hollow sphere cells. Direct contact of the cells was necessary for the differentiation of the solid sphere cells into mature hair cell-like cells.Conclusions: Cochlear sensory epithelium-derived progenitor cells require specific conditions to differentiate into mature hair cells.

scholarly journals A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Meenakshi Prajapati-DiNubila ◽  
Ana Benito-Gonzalez ◽  
Erin Jennifer Golden ◽  
Shuran Zhang ◽  
Angelika Doetzlhofer
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Hair Cells ◽  
Activin A ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Longitudinal Gradient ◽  
Hair Cell Differentiation ◽  
Local Gradient ◽  
Molecular Signals

The mammalian auditory sensory epithelium has one of the most stereotyped cellular patterns known in vertebrates. Mechano-sensory hair cells are arranged in precise rows, with one row of inner and three rows of outer hair cells spanning the length of the spiral-shaped sensory epithelium. Aiding such precise cellular patterning, differentiation of the auditory sensory epithelium is precisely timed and follows a steep longitudinal gradient. The molecular signals that promote auditory sensory differentiation and instruct its graded pattern are largely unknown. Here, we identify Activin A and its antagonist follistatin as key regulators of hair cell differentiation and show, using mouse genetic approaches, that a local gradient of Activin A signaling within the auditory sensory epithelium times the longitudinal gradient of hair cell differentiation. Furthermore, we provide evidence that Activin-type signaling regulates a radial gradient of terminal mitosis within the auditory sensory epithelium, which constitutes a novel mechanism for limiting the number of inner hair cells being produced.

scholarly journals Actin filaments, stereocilia, and hair cells of the bird cochlea. I. Length, number, width, and distribution of stereocilia of each hair cell are related to the position of the hair cell on the cochlea.

1983 ◽  
Vol 96 (3) ◽  
pp. 807-821 ◽  
Author(s):  
L G Tilney ◽  
J C Saunders
Keyword(s):  
Hair Cell ◽  
Surface Area ◽  
Hair Cells ◽  
Actin Filaments ◽  
Hexagonal Lattice ◽  
Frequency Discrimination ◽  
Sensory Epithelium ◽  
Scanning Microscopy ◽  
Apical Surface ◽  
Length Width

Located on the sensory epithelium of the sickle-shaped cochlea of a 7- to 10-d-old chick are approximately 5,000 hair cells. When the apical surface of these cell is examined by scanning microscopy, we find that the length, number, width, and distribution of the stereocilia on each hair cell are predetermined. Thus, a hair cell located at the distal end of the cochlea has 50 stereocilia, the longest of which are 5.5 microns in length and 0.12 microns in width, while those at the proximal end number 300 and are maximally 1.5 microns in length and 0.2 micron in width. In fact, if we travel along the cochlea from its distal to proximal end, we see that the stereocilia on successive hair cells gradually increase in number and width, yet decrease in length. Also, if we look transversely across the cochlea where adjacent hair cells have the same length and number of stereocilia (they are the same distance from the distal end of the cochlea), we find that the stereocilia of successive hair cells become thinner and that the apical surface area of the hair cell proper, not including the stereocilia, decreases from a maximum of 80 microns2 to 15 microns2. Thus, if we are told the length of the longest stereocilium on a hair cell and the width of that stereocilium, we can pinpoint the position of that hair cell on the cochlea in two axes. Likewise, if we are told the number of stereocilia and the apical surface of a hair cell, we can pinpoint the location of that cell in two axes. The distribution of the stereocilia on the apical surface of the cell is also precisely determined. More specifically, the stereocilia are hexagonally packed and this hexagonal lattice is precisely positioned relative to the kinocilium. Because of the precision with which individual hair cells regulate the length, width, number, and distribution of their cell extensions, we have a magnificent object with which to ask questions about how actin filaments that are present within the cell are regulated. Equally interesting is that the gradient in stereociliary length, number, width, and distribution may play an important role in frequency discrimination in the cochlea. This conclusion is amplified by the information presented in the accompanying paper (Tilney, L.G., E.H. Egelman, D.J. DeRosier, and J.C. Saunders, 1983, J. Cell Biol., 96:822-834) on the packing of actin filaments in this stereocilia.

scholarly journals SYSTEMIC KANAMYCIN TREATMENT HAS NO EFFECT ON CELL NUMBERS IN THE MOUSE UTRICULAR MACULA

2011 ◽  
Vol 24 (2) ◽  
pp. 69 ◽  
Author(s):  
Mette Kirkegaard ◽  
Stig Å Severinsen ◽  
Lise Wogensen ◽  
Jens R Nyengaard
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Caspase 3 ◽  
Cell Loss ◽  
Supporting Cell ◽  
Cell Number ◽  
Sensory Epithelium ◽  
Positive Staining ◽  
Survival Times ◽  
Cell Numbers

The aim of the present study is to estimate the total number of the sensory hair cells (chalice innervated and bouton innervated) and supporting cells in the mouse utricular sensory epithelium at two different time points after systemic kanamycin treatment. Mice were given two daily subcutaneous injections of kanamycin (600 or 900 mg/kg) for 15 consecutive days and allowed to survive either 1 or 3 weeks after end of treatment. Cell numbers were estimated using a physical fractionator. Paraffin-embedded tissue was immunohistochemically stained for active caspase-3 in order to detect apoptosis. There was no change in hair cell or supporting cell number after treatment with kanamycin and the survival time had no effect. Although no positive staining for caspase-3 was seen, hair cells with swollen chalices and dark stained nuclei were observed in the sensory epithelium of the treated animals, indicating some effect of the treatment. In conclusion, the dosing regime and survival times studied here are not sufficient to induce hair cell loss in the mouse utricle.

Notch signaling regulates the pattern of auditory hair cell differentiation in mammals

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3373-3383 ◽  
Author(s):  
A. Zine ◽  
T.R. Van De Water ◽  
F. de Ribaupierre
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Notch Signaling ◽  
Cell Fate ◽  
Hair Cells ◽  
Expression Patterns ◽  
Sensory Epithelium ◽  
Supporting Cells ◽  
Hair Cell Differentiation ◽  
Notch1 Signaling Pathway

The development of the mammalian cochlea is an example of patterning in the peripheral nervous system. Sensory hair cells and supporting cells in the cochlea differentiate via regional and cell fate specification. The Notch signaling components shows both distinct and overlapping expression patterns of Notch1 receptor and its ligands Jagged1 (Jag1) and Jagged2 (Jag2) in the developing auditory epithelium of the rat. On embryonic day 16 (E16), many precursor cells within the Kolliker's organ immunostained for the presence of both Notch1 and Jag1, while the area of hair cell precursors did not express either Notch1 and Jag1. During initial events of hair cell differentiation between E18 and birth, Notch1 and Jag1 expression predominated in supporting cells and Jag2 in nascent hair cells. Early after birth, Jag2 expression decreased in hair cells while the pattern of Notch1 expression now included both supporting cells and hair cells. We show that the normal pattern of hair cell differentiation is disrupted by alteration of Notch signaling. A decrease of either Notch1 or Jag1 expression by antisense oligonucleotides in cultures of the developing sensory epithelium resulted in an increase in the number of hair cells. Our data suggest that the Notch1 signaling pathway is involved in a complex interplay between the consequences of different ligand-Notch1 combinations during cochlear morphogenesis and the phases of hair cell differentiation.

scholarly journals Effect of hypodynamia on structure of vestibular apparatus in Japanese quail chicks: light microscopy

2011 ◽  
Vol 80 (1) ◽  
pp. 125-127
Author(s):  
Lenka Buričová ◽  
Peter Škrobánek ◽  
Magda Baranovská
Keyword(s):  
Light Microscopy ◽  
Inner Ear ◽  
Japanese Quail ◽  
Space Flight ◽  
Hair Cells ◽  
Simulated Microgravity ◽  
Morphological Changes ◽  
Sensory Epithelium ◽  
Vestibular Apparatus ◽  
Specific Impact

The model for studying the effects of simulated microgravity on the bird organism is hypodynamia. The aim of this study was to investigate the influence of chronic hypodynamia on the structure of the vestibular apparatus in Japanese quail by light microscopy. Morphological changes in the sensory epithelium of chicks reared under hypodynamia from 1 to 42 days of age were evaluated. The differences of shape and arrangement of hair cells in sensory epithelium macula utriculi and the dilatations on their basal parts were found in birds exposed to hypodynamia on day 14 and 42 compared to control. The results confirmed that hypodynamia has specific impact on developmental processes in Japanese quail and indicated that similar damage of inner ear sensory epithelium could be developed in chicks hatched and reared in conditions of real weightlessness during the space flight.

The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination

Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2495-2505 ◽  
Author(s):  
Ping Chen ◽  
Jane E. Johnson ◽  
Huda Y. Zoghbi ◽  
Neil Segil
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Cell Fate ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Proliferating Cells ◽  
Sensory Hair ◽  
Sensory Hair Cells ◽  
Hair Cell Differentiation

During embryonic development of the inner ear, the sensory primordium that gives rise to the organ of Corti from within the cochlear epithelium is patterned into a stereotyped array of inner and outer sensory hair cells separated from each other by non-sensory supporting cells. Math1, a close homolog of the Drosophila proneural gene atonal, has been found to be both necessary and sufficient for the production of hair cells in the mouse inner ear. Our results indicate that Math1 is not required to establish the postmitotic sensory primordium from which the cells of the organ of Corti arise, but instead is limited to a role in the selection and/or differentiation of sensory hair cells from within the established primordium. This is based on the observation that Math1 is only expressed after the appearance of a zone of non-proliferating cells that delineates the sensory primordium within the cochlear anlage. The expression of Math1 is limited to a subpopulation of cells within the sensory primordium that appear to differentiate exclusively into hair cells as the sensory epithelium matures and elongates through a process that probably involves radial intercalation of cells. Furthermore, mutation of Math1 does not affect the establishment of this postmitotic sensory primordium, even though the subsequent generation of hair cells is blocked in these mutants. Finally, in Math1 mutant embryos, a subpopulation of the cells within the sensory epithelium undergo apoptosis in a temporal gradient similar to the basal-to-apical gradient of hair cell differentiation that occurs in the cochlea of wild-type animals.

scholarly journals Expression and Localization of Ryanodine Receptors in the Frog Semicircular Canal

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Paola Perin ◽  
Laura Botta ◽  
Simona Tritto ◽  
Umberto Laforenza
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Semicircular Canal ◽  
Ryanodine Receptors ◽  
Cell Types ◽  
Sensory Epithelium ◽  
Rt Pcr ◽  
Supporting Cells ◽  
Vesicle Recycling ◽  
Ribbon Synapses

Several experiments suggest an important role for store-released Ca2+in hair cell organs: drugs targeting IP3and ryanodine (RyRs) receptors affect release from hair cells, and stores are thought to be involved in vesicle recycling at ribbon synapses. In this work we investigated the semicircular canal distribution of RyRs by immunofluorescence, using slice preparations of the sensory epithelium (to distinguish cell types) and flat mounts of the simpler nonsensory regions. RyRs were present in hair cells, mostly in supranuclear spots, but not in supporting cells; as regards nonsensory regions, they were also localized in dark cells and cells from the ductus. No labeling was found in nerve terminals, although nerve branches could be observed in proximity to hair cell RyR spots. The differential expression of RyR isoforms was studied by RT-PCR and immunoblotting, showing the presence of RyRαin both ampulla and canal arm and RyRβin the ampulla only.

scholarly journals Hair necessities: Hair cell differentiation and regeneration

2002 ◽  
Vol 24 (6) ◽  
pp. 9-11
Author(s):  
Matthew Holley
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Structural Diversity ◽  
Sensory Epithelium ◽  
Animal Kingdom ◽  
Hair Cell Differentiation ◽  
Human Hearing ◽  
Mechanosensory Hair Cells

Human hearing is governed by approximately 15 500 mechanosensory hair cells in each ear. These cells are located within the organ of Corti, the elongated auditory sensory epithelium that is stretched inside the coiled cochleae of the inner ear. Despite the structural diversity between the organs of hearing throughout the animal kingdom, hair cells are instantly recognizable. Their shapes and sizes vary considerably, but their apices carry a characteristic bundle of actin-filled stereocilia, or hairs, whose tips are connected by stretch-sensitive ‘tip-links’1. However, unlike most other animals, mammals do not regenerate lost hair cells2, consequently most forms of deafness are irreversible.

scholarly journals A Reversal in Hair Cell Orientation Organizes Both the Auditory and Vestibular Organs

2021 ◽  
Vol 15 ◽  
Author(s):  
Basile Tarchini
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Sensory Epithelium ◽  
Mirror Image ◽  
Hair Bundle ◽  
Directional Sensitivity ◽  
Mechanical Stimuli ◽  
Cell Orientation ◽  
Auditory Hair Cells ◽  
Organ Level

Sensory hair cells detect mechanical stimuli with their hair bundle, an asymmetrical brush of actin-based membrane protrusions, or stereocilia. At the single cell level, stereocilia are organized in rows of graded heights that confer the hair bundle with intrinsic directional sensitivity. At the organ level, each hair cell is precisely oriented so that its intrinsic directional sensitivity matches the direction of mechanical stimuli reaching the sensory epithelium. Coordinated orientation among neighboring hair cells usually ensures the delivery of a coherent local group response. Accordingly, hair cell orientation is locally uniform in the auditory and vestibular cristae epithelia in birds and mammals. However, an exception to this rule is found in the vestibular macular organs, and in fish lateral line neuromasts, where two hair cell populations show opposing orientations. This mirror-image hair cell organization confers bidirectional sensitivity at the organ level. Here I review our current understanding of the molecular machinery that produces mirror-image organization through a regional reversal of hair cell orientation. Interestingly, recent evidence suggests that auditory hair cells adopt their normal uniform orientation through a global reversal mechanism similar to the one at work regionally in macular and neuromast organs. Macular and auditory organs thus appear to be patterned more similarly than previously appreciated during inner ear development.

scholarly journals Activin signaling informs the graded pattern of terminal mitosis and hair cell differentiation in the mammalian cochlea

2018 ◽  
Author(s):  
Meenakshi Prajapati-DiNubila ◽  
Ana Benito-Gonzalez ◽  
Erin J. Golden ◽  
Shuran Zhang ◽  
Angelika Doetzlhofer
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Hair Cells ◽  
Activin A ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Longitudinal Gradient ◽  
Hair Cell Differentiation ◽  
Local Gradient ◽  
Molecular Signals

ABSTRACTThe mammalian auditory sensory epithelium has one of the most stereotyped cellular patterns known in vertebrates. Mechano-sensory hair cells are arranged in precise rows, with one row of inner and three rows of outer hair cells spanning the length of the spiral-shaped sensory epithelium. Aiding such precise cellular patterning, differentiation of the auditory sensory epithelium is precisely timed and follows a steep longitudinal gradient. The molecular signals that promote auditory sensory differentiation and instruct its graded pattern are largely unknown. Here, we identify Activin A as an activator of hair cell differentiation and show, using mouse genetic approaches, that a local gradient of Activin A signaling within the auditory sensory epithelium times the longitudinal gradient of hair cell differentiation. Furthermore, we provide evidence that Activin-type signaling regulates a radial gradient of terminal mitosis within the auditory sensory epithelium, which constitutes a novel mechanism for limiting the number of inner hair cells being produced.

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