Beyond generalized hair cells: Molecular cues for hair cell types

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.

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alms1 mutant zebrafish do not show hair cell phenotypes seen in other cilia mutants

10.1101/2020.11.13.381954 ◽

2020 ◽

Author(s):

Lauren Parkinson ◽

Tamara M. Stawicki

Keyword(s):

Hearing Loss ◽

Hair Cell ◽

Hair Cells ◽

Intraflagellar Transport ◽

Cell Loss ◽

Cell Types ◽

Mutant Mice ◽

Alström Syndrome ◽

Metabolic Defects ◽

Alstrom Syndrome

ABSTRACTMultiple cilia-associated genes have been shown to affect hair cells in zebrafish (Danio rerio), including the human deafness gene dcdc2, the radial spoke gene rsph9, and multiple intraflagellar transport (IFT) and transition zone genes. Recently a zebrafish alms1 mutant was generated. The ALMS1 gene is the gene mutated in the ciliopathy Alström Syndrome a disease that causes hearing loss among other symptoms. The hearing loss seen in Alström Syndrome may be due in part to hair cell defects as Alms1 mutant mice show stereocilia polarity defects and a loss of hair cells. Hair cell loss is also seen in postmortem analysis of Alström patients. The zebrafish alms1 mutant has metabolic defects similar to those seen in Alström syndrome and Alms1 mutant mice. We wished to investigate if it also had hair cell defects. We, however, failed to find any hair cell related phenotypes in alms1 mutant zebrafish. They had normal lateral line hair cell numbers as both larvae and adults and normal kinocilia formation. They also showed grossly normal swimming behavior, response to vibrational stimuli, and FM1-43 loading. Mutants also showed a normal degree of sensitivity to both short-term neomycin and long-term gentamicin treatment. These results indicate that cilia-associated genes differentially affect different hair cell types.

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Cnidarian hair cell development illuminates an ancient role for the class IV POU transcription factor in defining mechanoreceptor identity

eLife ◽

10.7554/elife.74336 ◽

2021 ◽

Vol 10 ◽

Author(s):

Ethan Ozment ◽

Arianna N Tamvacakis ◽

Jianhong Zhou ◽

Pablo Yamild Rosiles-Loeza ◽

Esteban Elías Escobar-Hernandez ◽

...

Keyword(s):

Transcription Factor ◽

Hair Cell ◽

Hair Cells ◽

Cell Types ◽

Sister Group ◽

Cell Development ◽

Developmental Genetics ◽

Sea Anemones ◽

Recognition Elements ◽

Class Iv

Although specialized mechanosensory cells are found across animal phylogeny, early evolutionary histories of mechanoreceptor development remain enigmatic. Cnidaria (e.g. sea anemones and jellyfishes) is the sister group to well-studied Bilateria (e.g. flies and vertebrates), and has two mechanosensory cell types - a lineage-specific sensory-effector known as the cnidocyte, and a classical mechanosensory neuron referred to as the hair cell. While developmental genetics of cnidocytes is increasingly understood, genes essential for cnidarian hair cell development are unknown. Here we show that the class IV POU homeodomain transcription factor (POU-IV) - an indispensable regulator of mechanosensory cell differentiation in Bilateria and cnidocyte differentiation in Cnidaria - controls hair cell development in the sea anemone cnidarian Nematostella vectensis. N. vectensis POU-IV is postmitotically expressed in tentacular hair cells, and is necessary for development of the apical mechanosensory apparatus, but not of neurites, in hair cells. Moreover, it binds to deeply conserved DNA recognition elements, and turns on a unique set of effector genes - including the transmembrane-receptor-encoding gene polycystin 1 - specifically in hair cells. Our results suggest that POU-IV directs differentiation of cnidarian hair cells and cnidocytes via distinct gene regulatory mechanisms, and support an evolutionarily ancient role for POU-IV in defining the mature state of mechanosensory neurons.

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Vestibular Type I and Type II Hair Cells. 1: Morphometric Identification in the Pigeon and Gerbil

Journal of Vestibular Research ◽

10.3233/ves-1997-7503 ◽

1997 ◽

Vol 7 (5) ◽

pp. 393-406

Author(s):

Anthony J. Ricci ◽

Katherine J. Rennie ◽

Stephen L. Cochran ◽

Golda A. Kevetter ◽

Manning J. Correia

Keyword(s):

Hair Cell ◽

Hair Cells ◽

Cell Types ◽

Type I ◽

Type Ii ◽

Body Width ◽

Fixed Tissue ◽

Neck Width ◽

I Cells ◽

Plate Width

Classically, type I and type II vestibular hair cells have been defined by their afferent innervation patterns. Little quantitative information exists on the intrinsic morphometric differences between hair cell types. Data presented here define a quantitative method for distinguishing hair cell types based on the morphometric properties of the hair cell’s neck region. The method is based initially on fixed histological sections, where hair cell types were identified by innervation pattern, type I cells having an afferent calyx. Cells were viewed using light microscopy, images were digitized, and measurements were made of the cell body width, the cuticular plate width, and the neck width. A plot of the ratio of the neck width to cuticular plate width (NPR) versus the ratio of the neck width to the body width (NBR) established four quadrants based on the best separation of type I and type II hair cells. The combination of the two variables made the accuracy of predicting either type I or type II hair cells greater than 90%. Statistical cluster analysis confirmed the quadrant separation. Similar analysis was performed on dissociated hair cells from semicircular canal, utricle, and lagena, giving results statistically similar to those of the fixed tissue. Additional comparisons were made between fixed tissue and isolated hair cells as well as across species (pigeon and gerbil) and between end organs (semicircular canal, utricle, and lagena). In each case, the same morphometric boundaries could be used to establish four quadrants, where quadrant 1 was predominantly type I cells and quadrant 3 was almost exclusively type II hair cells. The quadrant separations were confirmed statistically by cluster analysis. These data demonstrate that there are intrinsic morphometric differences between type I and type II hair cells and that these differences can be maintained when the hair cells are dissociated from their respective epithelia.

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Tmc Reliance Is Biased by the Hair Cell Subtype and Position Within the Ear

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.570486 ◽

2021 ◽

Vol 8 ◽

Author(s):

Shaoyuan Zhu ◽

Zongwei Chen ◽

Haoming Wang ◽

Brian M. McDermott

Keyword(s):

Hair Cell ◽

Hair Cells ◽

Cell Types ◽

Genetic Mutations ◽

Mechanical Stimuli ◽

Vestibular Organ ◽

Short Hair ◽

Transmembrane Channel ◽

Quantitative Measurements ◽

Cell Position

Hair cells are heterogenous, enabling varied roles in sensory systems. An emerging hypothesis is that the transmembrane channel-like (Tmc) proteins of the hair cell’s mechanotransduction apparatus vary within and between organs to permit encoding of different mechanical stimuli. Five anatomical variables that may coincide with different Tmc use by a hair cell within the ear are the containing organ, cell morphology, cell position within an organ, axis of best sensitivity for the cell, and the hair bundle’s orientation within this axis. Here, we test this hypothesis in the organs of the zebrafish ear using a suite of genetic mutations. Transgenesis and quantitative measurements demonstrate two morphologically distinct hair cell types in the central thickness of a vestibular organ, the lateral crista: short and tall. In contrast to what has been observed, we find that tall hair cells that lack Tmc1 generally have substantial reductions in mechanosensitivity. In short hair cells that lack Tmc2 isoforms, mechanotransduction is largely abated. However, hair cell Tmc dependencies are not absolute, and an exceptional class of short hair cell that depends on Tmc1 is present, termed a short hair cell erratic. To further test anatomical variables that may influence Tmc use, we map Tmc1 function in the saccule of mutant larvae that depend just on this Tmc protein to hear. We demonstrate that hair cells that use Tmc1 are found in the posterior region of the saccule, within a single axis of best sensitivity, and hair bundles with opposite orientations retain function. Overall, we determine that Tmc reliance in the ear is dependent on the organ, subtype of hair cell, position within the ear, and axis of best sensitivity.

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Cnidarian hair cell development illuminates an ancient role for the class IV POU transcription factor in defining mechanoreceptor identity

10.1101/2021.10.12.464036 ◽

2021 ◽

Author(s):

Ethan Ozment ◽

Arianna N. Tamvacakis ◽

Jianhong Zhou ◽

Pablo Yamild Rosiles-Loeza ◽

Esteban Elías Escobar-Hernandez ◽

...

Keyword(s):

Transcription Factor ◽

Hair Cell ◽

Hair Cells ◽

Cell Types ◽

Sister Group ◽

Cell Development ◽

Developmental Genetics ◽

Sea Anemones ◽

Recognition Elements ◽

Class Iv

Although specialized mechanosensory cells are found across animal phylogeny, early evolutionary histories of mechanoreceptor development remain enigmatic. Cnidaria (e.g. sea anemones and jellyfishes) is the sister group to well-studied Bilateria (e.g. flies and vertebrates), and has two mechanosensory cell types – a lineage-specific sensory-effector known as the cnidocyte, and a classical mechanosensory neuron referred to as the hair cell. While developmental genetics of cnidocytes is increasingly understood, genes essential for hair cell development are unknown. Here we show that the class IV POU homeodomain transcription factor (POU-IV) – an indispensable regulator of mechanosensory cell differentiation in Bilateria and cnidocyte differentiation in Cnidaria – controls hair cell development in the sea anemone cnidarian Nematostella vectensis. N. vectensis POU-IV is postmitotically expressed in tentacular hair cells, and is necessary for development of the apical mechanosensory apparatus, but not of neurites, in hair cells. Moreover, it binds to deeply conserved DNA recognition elements, and turns on a unique set of effector genes – including the transmembrane-receptor-encoding gene polycystin 1 – specifically in hair cells. Our results suggest that POU-IV directs differentiation of cnidarian hair cells and cnidocytes via distinct gene regulatory mechanisms, and support an evolutionarily ancient role for POU-IV in defining the mature state of mechanosensory neurons.

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Stiffness and tension gradients of the hair cell’s tip-link complex in the mammalian cochlea

eLife ◽

10.7554/elife.43473 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 13

Author(s):

Mélanie Tobin ◽

Atitheb Chaiyasitdhi ◽

Vincent Michel ◽

Nicolas Michalski ◽

Pascal Martin

Keyword(s):

Hair Cell ◽

Hair Cells ◽

Frequency Tuning ◽

Cell Types ◽

Outer Hair Cells ◽

Tip Link ◽

Biophysical Mechanism ◽

Apical Half ◽

Mechanosensory Hair Cells ◽

The Brain

Sound analysis by the cochlea relies on frequency tuning of mechanosensory hair cells along a tonotopic axis. To clarify the underlying biophysical mechanism, we have investigated the micromechanical properties of the hair cell’s mechanoreceptive hair bundle within the apical half of the rat cochlea. We studied both inner and outer hair cells, which send nervous signals to the brain and amplify cochlear vibrations, respectively. We find that tonotopy is associated with gradients of stiffness and resting mechanical tension, with steeper gradients for outer hair cells, emphasizing the division of labor between the two hair-cell types. We demonstrate that tension in the tip links that convey force to the mechano-electrical transduction channels increases at reduced Ca2+. Finally, we reveal gradients in stiffness and tension at the level of a single tip link. We conclude that mechanical gradients of the tip-link complex may help specify the characteristic frequency of the hair cell.

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alms1 mutant zebrafish do not show hair cell phenotypes seen in other cilia mutants

PLoS ONE ◽

10.1371/journal.pone.0246844 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0246844

Author(s):

Lauren Parkinson ◽

Tamara M. Stawicki

Keyword(s):

Hearing Loss ◽

Hair Cell ◽

Hair Cells ◽

Intraflagellar Transport ◽

Cell Loss ◽

Cell Types ◽

Mutant Mice ◽

Alström Syndrome ◽

Metabolic Defects ◽

Alstrom Syndrome

Multiple cilia-associated genes have been shown to affect hair cells in zebrafish (Danio rerio), including the human deafness gene dcdc2, the radial spoke gene rsph9, and multiple intraflagellar transport (IFT) and transition zone genes. Recently a zebrafish alms1 mutant was generated. The ALMS1 gene is the gene mutated in the ciliopathy Alström Syndrome a disease that causes hearing loss among other symptoms. The hearing loss seen in Alström Syndrome may be due in part to hair cell defects as Alms1 mutant mice show stereocilia polarity defects and a loss of hair cells. Hair cell loss is also seen in postmortem analysis of Alström patients. The zebrafish alms1 mutant has metabolic defects similar to those seen in Alström syndrome and Alms1 mutant mice. We wished to investigate if it also had hair cell defects. We, however, failed to find any hair cell related phenotypes in alms1 mutant zebrafish. They had normal lateral line hair cell numbers as both larvae and adults and normal kinocilia formation. They also showed grossly normal swimming behavior, response to vibrational stimuli, and FM1-43 loading. Mutants also showed a normal degree of sensitivity to both short-term neomycin and long-term gentamicin treatment. These results indicate that cilia-associated genes differentially affect different hair cell types.

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Autocorrelation Analysis of Hair Bundle Structure in the Utricle

Journal of Neurophysiology ◽

10.1152/jn.00565.2006 ◽

2006 ◽

Vol 96 (5) ◽

pp. 2653-2669 ◽

Cited By ~ 18

Author(s):

M. H. Rowe ◽

E. H. Peterson

Keyword(s):

Hair Cell ◽

Hair Cells ◽

Cell Types ◽

Head Movements ◽

Type I ◽

Autocorrelation Analysis ◽

Response Dynamics ◽

Hair Bundles ◽

Vestibular Organs ◽

Bundle Structure

The ability of hair bundles to signal head movements and sounds depends significantly on their structure, but a quantitative picture of bundle structure has proved elusive. The problem is acute for vestibular organs because their hair bundles exhibit complex morphologies that vary with endorgan, hair cell type, and epithelial locus. Here we use autocorrelation analysis to quantify stereociliary arrays (the number, spacing, and distribution of stereocilia) on hair cells of the turtle utricle. Our first goal was to characterize zonal variation across the macula, from medial extrastriola, through striola, to lateral extrastriola. This is important because it may help explain zonal variation in response dynamics of utricular hair cells and afferents. We also use known differences in type I and II bundles to estimate array characteristics of these two hair cell types. Our second goal was to quantify variation in array orientation at single macular loci and use this to estimate directional tuning in utricular afferents. Our major findings are that, of the features measured, array width is the most distinctive feature of striolar bundles, and within the striola there are significant, negatively correlated gradients in stereocilia number and spacing that parallel gradients in bundle heights. Together with previous results on stereocilia number and bundle heights, our results support the hypothesis that striolar hair cells are specialized to signal high-frequency/acceleration head movements. Finally, there is substantial variation in bundle orientation at single macular loci that may help explain why utricular afferents respond to stimuli orthogonal to their preferred directions.

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scRNA-Seq reveals distinct stem cell populations that drive hair cell regeneration after loss of Fgf and Notch signaling

eLife ◽

10.7554/elife.44431 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 36

Author(s):

Mark E Lush ◽

Daniel C Diaz ◽

Nina Koenecke ◽

Sungmin Baek ◽

Helena Boldt ◽

...

Keyword(s):

Hair Cell ◽

Notch Signaling ◽

Lateral Line ◽

Hair Cells ◽

Cell Types ◽

Developmental Trajectory ◽

Cell Regeneration ◽

Hair Cell Regeneration ◽

Organ Regeneration ◽

Hair Cell Differentiation

Loss of sensory hair cells leads to deafness and balance deficiencies. In contrast to mammalian hair cells, zebrafish ear and lateral line hair cells regenerate from poorly characterized support cells. Equally ill-defined is the gene regulatory network underlying the progression of support cells to differentiated hair cells. scRNA-Seq of lateral line organs uncovered five different support cell types, including quiescent and activated stem cells. Ordering of support cells along a developmental trajectory identified self-renewing cells and genes required for hair cell differentiation. scRNA-Seq analyses of fgf3 mutants, in which hair cell regeneration is increased, demonstrates that Fgf and Notch signaling inhibit proliferation of support cells in parallel by inhibiting Wnt signaling. Our scRNA-Seq analyses set the foundation for mechanistic studies of sensory organ regeneration and is crucial for identifying factors to trigger hair cell production in mammals. The data is searchable and publicly accessible via a web-based interface.

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