Key Points
Hair cells are the specialized mechanoreceptors of the inner ear.
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Many of the genes that underlie the morphogenesis of hair cells have been identified through positional cloning of hereditary hearing loss disorders.
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Rearrangement of actin filaments is a hallmark of the developmental transition of a microvillus into a stereocilium, the hair cell's mechanosensitive organelle.
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Hair cells use actin-binding proteins and unconventional myosins to form and maintain the characteristic shape of a stereocilium, which is required for mechanosensitivity.
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The precise arrangement of stereocilia into a cohesive 'hair' bundle is also required for mechanosensitivity.
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Hair-bundle cohesion is mediated by ultrastructural links between adjacent stereocilia.
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Hair cells have adapted molecular mechanisms of intercellular adhesion to mediate hair-bundle cohesion.
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Programmed differential elongation of stereocilia produces the staircase-like configuration of the hair bundle.
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Mechanoreceptor current might be required for morphogenesis of the hair bundle.
Abstract
The mammalian inner ear is a sensory organ that has specialized hair cells that detect sound, as well as orientation and movement of the head. The 'hair' bundle on the apical surface of these cells is a mechanosensitive organelle that consists of precisely organized actin-filled projections known as stereocilia. Alterations in hair-bundle morphogenesis can result in hearing loss, balance defects or both. Positional cloning of genes that underlie hereditary hearing loss, coupled with the characterization of corresponding mouse models, is revealing how hair cells have adapted the molecular mechanisms of intracellular motility and intercellular adhesion for the morphogenesis of their apical surfaces.
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Acknowledgements
We thank P. Belyantsev for the drawings and movies, R. Leapman for providing access to electron microscopy instruments, E. Boger for helpful discussions, and D. Drayna, R. Morell, M. Kelley and D. Wu for critically reading the manuscript. Work in the laboratories of T.B.F. and A.J.G. was supported by intramural research funds from the National Institute on Deafness and Other Communication Disorders.
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Glossary
- STEREOCILIUM
-
(Pl. stereocilia). A large, rigid, actin-filled microvillus on the apical surface of hair cells in the inner ear.
- ECTODERM
-
Embryonic tissue that is the precursor of the epidermis and the nervous system.
- MICROVILLUS
-
(Pl. microvilli). A thin, cylindrical, membrane-covered projection on the surface of an animal cell that contains a core bundle of actin filaments.
- ACTIN FILAMENT
-
A helical protein filament that is formed by the polymerization of globular actin molecules.
- VESTIBULAR AREFLEXIA
-
An abnormal absent response to artificial caloric (hot or cold) stimulation of the neurosensory organs of balance in the inner ear.
- FILOPODIUM
-
(Pl. filopodia). A thin, spike-like protrusion with an actin filament core that is generated on the leading edge of a motile animal cell.
- SENSORINEURAL HEARING LOSS
-
Hearing loss that results from abnormalities of the inner ear or auditory neural pathways.
- MECHANOTRANSDUCTION
-
Conversion of a mechanical stimulus, such as sound, into an electrochemical signal.
- PLANAR-CELL POLARITY
-
The polarized organization of cells in the plane of an epithelium.
- CALCIUM CHELATORS
-
Substances that reversibly bind calcium, usually with high affinity, to remove free calcium ions from a solution.
- RETINITIS PIGMENTOSA
-
An aetiologically heterogeneous disorder that is characterized by progressive loss of vision and retinal photoreceptor degeneration.
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Frolenkov, G., Belyantseva, I., Friedman, T. et al. Genetic insights into the morphogenesis of inner ear hair cells. Nat Rev Genet 5, 489–498 (2004). https://doi.org/10.1038/nrg1377
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DOI: https://doi.org/10.1038/nrg1377
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Tprn is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice
Frontiers of Medicine (2019)
