scholarly journals Determination and Commitment of Mechanosensory Hair Cells

2002 ◽  
Vol 2 ◽  
pp. 1079-1094 ◽  
Author(s):  
Matthew W. Kelley
Keyword(s):  
Hair Cell ◽  
Signaling Pathways ◽  
Hair Cells ◽  
Progenitor Cell ◽  
Supporting Cells ◽  
Cell Identity ◽  
Final Choice ◽  
Sensory Epithelia ◽  
Cellular Factors ◽  
Mechanosensory Hair Cells

Sound and movement are perceived through the vibration of modified ciliary bundles located on the apical surfaces of specialized mechanosensory hair cells. These hair cells derive from specific regions of the otocyst that become determined to develop initially as sensory epithelia and ultimately as either hair cells or supporting cells. The number of hair cells in an individual vertebrate is surprisingly small and the ability to replace these cells varies among different classes. The molecular and cellular factors that specify hair cell identity are not known, but the results of recent experiments have begun to identify some of the signaling pathways that play important roles in hair cell development. This review will describe recent findings related to the factors that influence the final choice of a progenitor cell to develop as a hair cell and discuss their implications for the overall development of the auditory and vestibular systems.

scholarly journals β-Catenin is required for radial cell patterning and identity in the developing mouse cochlea

2019 ◽  
Vol 116 (42) ◽  
pp. 21054-21060 ◽  
Author(s):  
Lina Jansson ◽  
Michael Ebeid ◽  
Jessica W. Shen ◽  
Tara E. Mokhtari ◽  
Lee A. Quiruz ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Hair Cell ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Supporting Cells ◽  
Aberrant Expression ◽  
Cell Identity ◽  
Pillar Cell ◽  
Radial Patterning

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.

scholarly journals Regenerating hair cells in vestibular sensory epithelia from humans

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ruth Rebecca Taylor ◽  
Anastasia Filia ◽  
Ursula Paredes ◽  
Yukako Asai ◽  
Jeffrey R Holt ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Viral Vector ◽  
Explant Culture ◽  
Marker Genes ◽  
Cell Marker ◽  
Supporting Cells ◽  
Sensory Epithelia ◽  
Myosin Viia ◽  
Vestibular Sensory Epithelia

Human vestibular sensory epithelia in explant culture were incubated in gentamicin to ablate hair cells. Subsequent transduction of supporting cells with ATOH1 using an Ad-2 viral vector resulted in generation of highly significant numbers of cells expressing the hair cell marker protein myosin VIIa. Cells expressing myosin VIIa were also generated after blocking the Notch signalling pathway with TAPI-1 but less efficiently. Transcriptomic analysis following ATOH1 transduction confirmed up-regulation of 335 putative hair cell marker genes, including several downstream targets of ATOH1. Morphological analysis revealed numerous cells bearing dense clusters of microvilli at the apical surfaces which showed some hair cell-like characteristics confirming a degree of conversion of supporting cells. However, no cells bore organised hair bundles and several expected hair cell markers genes were not expressed suggesting incomplete differentiation. Nevertheless, the results show a potential to induce conversion of supporting cells in the vestibular sensory tissues of humans.

Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4637-4644 ◽  
Author(s):  
C. Haddon ◽  
Y.J. Jiang ◽  
L. Smithers ◽  
J. Lewis
Keyword(s):  
Cell Differentiation ◽  
Lateral Inhibition ◽  
Hair Cells ◽  
Sensory Cell ◽  
Cell Types ◽  
Notch Signalling ◽  
Supporting Cells ◽  
Fine Grained ◽  
Mechanosensory Hair Cells ◽  
The Mind

Mechanosensory hair cells in the sensory patches of the vertebrate ear are interspersed among supporting cells, forming a fine-grained pattern of alternating cell types. Analogies with Drosophila mechanosensory bristle development suggest that this pattern could be generated through lateral inhibition mediated by Notch signalling. In the zebrafish ear rudiment, homologues of Notch are widely expressed, while the Delta homologues deltaA, deltaB and deltaD, coding for Notch ligands, are expressed in small numbers of cells in regions where hair cells are soon to differentiate. This suggests that the delta-expressing cells are nascent hair cells, in agreement with findings for Delta1 in the chick. According to the lateral inhibition hypothesis, the nascent hair cells, by expressing Delta protein, would inhibit their neighbours from becoming hair cells, forcing them to be supporting cells instead. The zebrafish mind bomb mutant has abnormalities in the central nervous system, somites, and elsewhere, diagnostic of a failure of Delta-Notch signalling: in the CNS, it shows a neurogenic phenotype accompanied by misregulated delta gene expression. Similar misregulation of delta; genes is seen in the ear, along with misregulation of a Serrate homologue, serrateB, coding for an alternative Notch ligand. Most dramatically, the sensory patches in the mind bomb ear consist solely of hair cells, which are produced in great excess and prematurely; at 36 hours post fertilization, there are more than ten times as many as normal, while supporting cells are absent. A twofold increase is seen in the number of otic neurons also. The findings are strong evidence that lateral inhibition mediated by Delta-Notch signalling controls the pattern of sensory cell differentiation in the ear.

On the Legacy of Genetically Altered Mouse Models to Explore Vestibular Function: Distribution of Vestibular Hair Cell Phenotypes in the Otoferlin-Null Mouse

2019 ◽  
Vol 128 (6_suppl) ◽  
pp. 125S-133S ◽  
Author(s):  
Terry J. Prins ◽  
Johnny J. Saldate ◽  
Gerald S. Berke ◽  
Larry F. Hoffman
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Vestibular Function ◽  
Null Mouse ◽  
Type I ◽  
Vestibular Hypofunction ◽  
Cellular Changes ◽  
Sensory Epithelia ◽  
Vestibular Sensory Epithelia ◽  
Cell Phenotypes

Objectives: Early in his career, David Lim recognized the scientific impact of genetically anomalous mice exhibiting otoconia agenesis as models of drastically compromised vestibular function. While these studies focused on the mutant pallid mouse, contemporary genetic tools have produced other models with engineered functional modifications. Lim and colleagues foresaw the need to analyze vestibular epithelia from pallid mice to verify the absence of downstream consequences that might be secondary to the altered load represented by otoconial agenesis. More generally, however, such comparisons also contribute to an understanding of the susceptibility of labyrinthine sensory epithelia to more widespread cellular changes associated with what may appear as isolated modifications. Methods: Our laboratory utilizes a model of vestibular hypofunction produced through genetic alteration, the otoferlin-null mouse, which has been shown to exhibit severely compromised stimulus-evoked neurotransmitter release in type I hair cells of the utricular striola. The present study, reminiscent of early investigations of Lim and colleagues that explored the utility of a genetically altered mouse to explore its utility as a model of vestibular hypofunction, endeavored to compare the expression of the hair cell marker oncomodulin in vestibular epithelia from wild-type and otoferlin-null mice. Results: We found that levels of oncomodulin expression were much greater in type I than type II hair cells, though were similar across the 3 genotypes examined (ie, including heterozygotes). Conclusion: These findings support the notion that modifications resulting in a specific component of vestibular hypofunction are not accompanied by widespread morphologic and cellular changes in the vestibular sensory epithelia.

scholarly journals LIN28B/let-7control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling

2020 ◽  
Vol 117 (36) ◽  
pp. 22225-22236
Author(s):  
Xiao-Jun Li ◽  
Angelika Doetzlhofer
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Rna Binding ◽  
Mammalian Target Of Rapamycin ◽  
Cell Loss ◽  
Supporting Cell ◽  
Dependent Manner ◽  
Cell Plasticity ◽  
Supporting Cells ◽  
Cochlear Hair Cells

Mechano-sensory hair cells within the inner ear cochlea are essential for the detection of sound. In mammals, cochlear hair cells are only produced during development and their loss, due to disease or trauma, is a leading cause of deafness. In the immature cochlea, prior to the onset of hearing, hair cell loss stimulates neighboring supporting cells to act as hair cell progenitors and produce new hair cells. However, for reasons unknown, such regenerative capacity (plasticity) is lost once supporting cells undergo maturation. Here, we demonstrate that the RNA binding protein LIN28B plays an important role in the production of hair cells by supporting cells and provide evidence that the developmental drop in supporting cell plasticity in the mammalian cochlea is, at least in part, a product of declining LIN28B-mammalian target of rapamycin (mTOR) activity. Employing murine cochlear organoid and explant cultures to model mitotic and nonmitotic mechanisms of hair cell generation, we show that loss of LIN28B function, due to its conditional deletion, or due to overexpression of the antagonistic miRNAlet-7g, suppressed Akt-mTOR complex 1 (mTORC1) activity and renders young, immature supporting cells incapable of generating hair cells. Conversely, we found that LIN28B overexpression increased Akt-mTORC1 activity and allowed supporting cells that were undergoing maturation to de-differentiate into progenitor-like cells and to produce hair cells via mitotic and nonmitotic mechanisms. Finally, using the mTORC1 inhibitor rapamycin, we demonstrate that LIN28B promotes supporting cell plasticity in an mTORC1-dependent manner.

scholarly journals Aquaporin-6 Expression in the Cochlear Sensory Epithelium Is Downregulated by Salicylates

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Paola Perin ◽  
Simona Tritto ◽  
Laura Botta ◽  
Jacopo Maria Fontana ◽  
Giulia Gastaldi ◽  
...  
Keyword(s):  
Inner Ear ◽  
Expression Pattern ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Rt Pcr ◽  
Supporting Cells ◽  
Sensory Epithelia ◽  
Mechanical Compliance

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.

Structure and Development of Vestibular Hair Cells in the Larval Bullfrog

1979 ◽  
Vol 88 (3) ◽  
pp. 427-437 ◽  
Author(s):  
Cheuk W. Li ◽  
Edwin R. Lewis
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
High Frequency ◽  
Low Frequency ◽  
Type A ◽  
Cell Types ◽  
Sensory Organs ◽  
Sensory Epithelia ◽  
Sensory Structures ◽  
Vestibular Organs

Structure and development of hair cells in vestibular sensory organs of the larval bullfrog were examined with scanning electron microscopy. The larval vestibular sensory epithelia resembled those of the adult frog. Based on morphology of the ciliary tufts, seven hair cell types were identified. One of them, the type A hair cell, appears to be the morphogenetic precursor of other hair cell types. The size of the stereocilia of type A hair cells is comparable to the surrounding microvilli. The distribution of immature type A hair cells suggests that the periphery of the sensory epithelia is the principal growth zone and the site of formation of new hair cells. However, a far greater number of type A hair cells were found in high frequency sensitive sensory organs (sacculus, amphibian and basilar papillae) than low frequency sensitive vestibular sensory structures (canal cristae, utriculus and lagena). This phenomenon may suggest that the time period required for the maturation of type A hair cells to their ultimate hair cell types in the low frequency sensitive vestibular organs is shorter than in the high frequency sensory structures. It is also possible that the low frequency sensitive vestibular organs may have completed their morphogenetic development in the early larval stages, while morphogenesis of hair cells in the high frequency sensory structures continues throughout the lifetime of a bullfrog.

scholarly journals The cell biology of hearing

2010 ◽  
Vol 190 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Martin Schwander ◽  
Bechara Kachar ◽  
Ulrich Müller
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Cell Biology ◽  
Cell Development ◽  
Biological Mechanisms ◽  
Electrical Signals ◽  
Mechanosensory Hair Cells

Mammals have an astonishing ability to sense and discriminate sounds of different frequencies and intensities. Fundamental for this process are mechanosensory hair cells in the inner ear that convert sound-induced vibrations into electrical signals. The study of genes that are linked to deafness has provided insights into the cell biological mechanisms that control hair cell development and their function as mechanosensors.

scholarly journals Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space

2019 ◽  
Author(s):  
Travis A. Babola ◽  
Calvin J. Kersbergen ◽  
Han Chin Wang ◽  
Dwight E. Bergles
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Extracellular Space ◽  
Molecular Mechanisms ◽  
Purinergic Signaling ◽  
Burst Firing ◽  
Supporting Cells ◽  
Cell Excitability ◽  
Sensory Pathways ◽  
Cochlear Supporting Cells

AbstractNeurons in developing sensory pathways exhibit spontaneous bursts of electrical activity that are critical for survival, maturation and circuit refinement. In the auditory system, intrinsically generated activity arises within the cochlea, but the molecular mechanisms that initiate this activity remain poorly understood. We show that burst firing of mouse inner hair cells prior to hearing onset requires P2RY1 autoreceptors expressed by inner supporting cells. P2RY1 activation triggers K+ efflux and depolarization of hair cells, as well as osmotic shrinkage of supporting cells that dramatically increased the extracellular space and speed of K+ redistribution. Pharmacological inhibition or genetic disruption of P2RY1 suppressed neuronal burst firing by reducing K+ release, but unexpectedly enhanced their tonic firing, as water resorption by supporting cells reduced the extracellular space, slowing K+ clearance. These studies indicate that purinergic signaling in supporting cells regulates hair cell excitability by controlling the volume of the extracellular space.

scholarly journals Conserved and Divergent Principles of Planar Polarity Revealed by Hair Cell Development and Function

2021 ◽  
Vol 15 ◽  
Author(s):  
Michael R. Deans
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Model Organism ◽  
Vestibular Function ◽  
Sensory Receptor ◽  
Apical Surface ◽  
Planar Polarity ◽  
Vestibular Hair Cells ◽  
Sensory Epithelia

Planar polarity describes the organization and orientation of polarized cells or cellular structures within the plane of an epithelium. The sensory receptor hair cells of the vertebrate inner ear have been recognized as a preeminent vertebrate model system for studying planar polarity and its development. This is principally because planar polarity in the inner ear is structurally and molecularly apparent and therefore easy to visualize. Inner ear planar polarity is also functionally significant because hair cells are mechanosensors stimulated by sound or motion and planar polarity underlies the mechanosensory mechanism, thereby facilitating the auditory and vestibular functions of the ear. Structurally, hair cell planar polarity is evident in the organization of a polarized bundle of actin-based protrusions from the apical surface called stereocilia that is necessary for mechanosensation and when stereociliary bundle is disrupted auditory and vestibular behavioral deficits emerge. Hair cells are distributed between six sensory epithelia within the inner ear that have evolved unique patterns of planar polarity that facilitate auditory or vestibular function. Thus, specialized adaptations of planar polarity have occurred that distinguish auditory and vestibular hair cells and will be described throughout this review. There are also three levels of planar polarity organization that can be visualized within the vertebrate inner ear. These are the intrinsic polarity of individual hair cells, the planar cell polarity or coordinated orientation of cells within the epithelia, and planar bipolarity; an organization unique to a subset of vestibular hair cells in which the stereociliary bundles are oriented in opposite directions but remain aligned along a common polarity axis. The inner ear with its complement of auditory and vestibular sensory epithelia allows these levels, and the inter-relationships between them, to be studied using a single model organism. The purpose of this review is to introduce the functional significance of planar polarity in the auditory and vestibular systems and our contemporary understanding of the developmental mechanisms associated with organizing planar polarity at these three cellular levels.

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