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

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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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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Role of the POU-Domain Transcription Factor Brn-3.1 in Hair Cell Development

Cell and Molecular Biology of the Ear ◽

10.1007/978-1-4615-4223-0_8 ◽

2000 ◽

pp. 113-119

Author(s):

Allen F. Ryan

Keyword(s):

Transcription Factor ◽

Hair Cell ◽

Cell Development ◽

Pou Domain

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Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells

Development ◽

10.1242/dev.125.4.557 ◽

1998 ◽

Vol 125 (4) ◽

pp. 557-566 ◽

Cited By ~ 3

Author(s):

T. Self ◽

M. Mahony ◽

J. Fleming ◽

J. Walsh ◽

S.D. Brown ◽

...

Keyword(s):

Hair Cell ◽

Hair Cells ◽

Usher Syndrome ◽

Orthologous Gene ◽

Cell Development ◽

Cochlear Hair Cells ◽

Cochlear Hair Cell ◽

Show Evidence ◽

Myosin Viia ◽

And Function

The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.

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A Critical E-box in Barhl1 3′ Enhancer Is Essential for Auditory Hair Cell Differentiation

Cells ◽

10.3390/cells8050458 ◽

2019 ◽

Vol 8 (5) ◽

pp. 458 ◽

Cited By ~ 2

Author(s):

Kun Hou ◽

Hui Jiang ◽

Md. Rezaul Karim ◽

Chao Zhong ◽

Zhouwen Xu ◽

...

Keyword(s):

Cell Differentiation ◽

Hair Cell ◽

Hair Cells ◽

Embryonic Stem ◽

Cell Development ◽

Homologous Gene ◽

Auditory Hair Cells ◽

E Box ◽

Hair Cell Differentiation

Barhl1, a mouse homologous gene of Drosophila BarH class homeobox genes, is highly expressed within the inner ear and crucial for the long-term maintenance of auditory hair cells that mediate hearing and balance, yet little is known about the molecular events underlying Barhl1 regulation and function in hair cells. In this study, through data mining and in vitro report assay, we firstly identified Barhl1 as a direct target gene of Atoh1 and one E-box (E3) in Barhl1 3’ enhancer is crucial for Atoh1-mediated Barhl1 activation. Then we generated a mouse embryonic stem cell (mESC) line carrying disruptions on this E3 site E-box (CAGCTG) using CRISPR/Cas9 technology and this E3 mutated mESC line is further subjected to an efficient stepwise hair cell differentiation strategy in vitro. Disruptions on this E3 site caused dramatic loss of Barhl1 expression and significantly reduced the number of induced hair cell-like cells, while no affections on the differentiation toward early primitive ectoderm-like cells and otic progenitors. Finally, through RNA-seq profiling and gene ontology (GO) enrichment analysis, we found that this E3 box was indispensable for Barhl1 expression to maintain hair cell development and normal functions. We also compared the transcriptional profiles of induced cells from CDS mutated and E3 mutated mESCs, respectively, and got very consistent results except the Barhl1 transcript itself. These observations indicated that Atoh1-mediated Barhl1 expression could have important roles during auditory hair cell development. In brief, our findings delineate the detail molecular mechanism of Barhl1 expression regulation in auditory hair cell differentiation.

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Structure and Development of Vestibular Hair Cells in the Larval Bullfrog

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348947908800323 ◽

1979 ◽

Vol 88 (3) ◽

pp. 427-437 ◽

Cited By ~ 23

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.

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The cell biology of hearing

The Journal of Cell Biology ◽

10.1083/jcb.201001138 ◽

2010 ◽

Vol 190 (1) ◽

pp. 9-20 ◽

Cited By ~ 166

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.

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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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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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