Sensory regeneration in the vertebrate inner ear: Differences at the levels of cells and species

https://doi.org/10.1016/j.heares.2010.05.004Get rights and content

Abstract

The ears of nonmammalian vertebrates are capable of regenerating sensory hair cells after acoustic trauma or ototoxic injury. In contrast, the mammalian inner ear lacks regenerative ability and the loss of hair cells results in permanent deficits in hearing and balance. Comparative observations across all vertebrate classes suggest that regenerative ability was a stem trait and was lost during the course of mammalian evolution. This review provides an overview of regeneration and post-embryonic growth in the vertebrate ear. It is suggested that the lack of regeneration in the mammalian ear was the result of a trade-off between phenotypic plasticity of supporting cells and sensitive high frequency hearing.

Introduction

Hair cells transduce mechanical stimuli caused by head motions and sound vibrations into changes in membrane potential, ultimately leading to modulation in the firing rate of auditory and vestibular neurons. The presence of functional hair cells is necessary for both normal hearing and maintenance of postural equilibrium. In birds and mammals, a full complement of sensory hair cells is produced during embryogenesis. In contrast, the ears of fish and amphibians continue to add hair cells throughout life. All nonmammalian vertebrates appear to be capable of regenerating hair cells after injury (e.g., acoustic trauma or aminoglycoside ototoxicity). The relatively simple structure of the ears of most nonmammalian vertebrates, combined with their continued growth throughout life and their patterns of hair cell turnover, is likely to be permissive for the production of replacement hair cells in the mature ear. The ability to regenerate hair cells was lost during the evolution of the mammalian ear, for reasons that remain unknown. Nevertheless, the unique structure and function of the mammalian inner ear permits us to make some informed speculations about the underlying reasons for its lack of regenerative ability.

The sensory epithelia of all vertebrae ears are comprised of two general cell phenotypes: hair cells and supporting cells. Regeneration (when it occurs) is mediated by the proliferation or transdifferentiation of supporting cells (reviewed by Brigande and Heller, 2009). In general, the regenerative ability of a particular hair cell sensory organ is closely linked with the proliferative ability of its resident supporting cells. This implies that the loss of a hair cell may lead to the partial dedifferentiation of an adjoining supporting cell, allowing that cell to either divide and produce hair cell progeny or directly re-differentiate as a new hair cell. Most nonmammalian ears appear to use a combination of these two mechanisms during the regenerative process (e.g., Brignull et al., 2009), and a complete understanding of the differing regenerative abilities of the vertebrate ear will probably require identification of the specific genes and signaling pathways that regulate cell cycle entry and phenotypic maintenance in supporting cells.

Section snippets

Phylogenetic differences in hair cell regeneration: an overview

The vertebrate ear is comprised of sensory organs that are specialized for either motion detection or hearing. Vestibular sensory organs are present in all vertebrates and possess relatively similar morphologies, even in widely divergent species. In contrast, the structure and function of the various sensory organs for hearing (i.e., the amphibian papilla, basilar papilla, cochlea) shows considerable diversity, and these differences are accompanied by differences in regenerative ability.

Ongoing hair cell turnover is very common among nonmammalian vertebrates

Many hair cells in the mammalian ear are capable of surviving for an animal’s entire life span (which can exceed 80–90 years in humans). One surprising feature of the ears of many nonmammalian species is that their hair cells have relatively short life spans. Hair cells in the avian vestibular organs, for example, appear to live for several months, at which point they undergo spontaneous apoptosis and are replaced via the proliferation of supporting cells. For this reason, the vestibular organs

Structural correlates of regenerative ability in the ears of birds and mammals

As noted above, the hearing organs of birds and mammals have very different regenerative abilities. Hair cells in the avian basilar papilla quickly regenerate after noise damage or aminoglycoside ototoxicity, while the mammalian organ of Corti appears to be completely incapable of replacing lost hair cells. Although the biological basis of this difference is not known, it is probably related to the very different morphologies of those sensory organs. In cross-section, the sensory epithelium of

Robust regenerative ability is probably the ‘default’ condition of the vertebrate ear and has been lost in mammals

Taken together, the studies described here suggest that the ability to regenerate hair cells is widespread amongst vertebrates and is absent only in mammals. Given the phylogeny of the vertebrate ear, it is likely that regenerative ability was the norm for most of the ear’s evolutionary history and has been retained in four of the five vertebrate classes. Questions concerning sensory regeneration are impossible to resolve through fossil evidence, and existing molecular data have not yet

Acknowledgements

Regeneration research in the author’s lab is supported by grant DC006283 from the NIDCD/NIH. Additional support for imaging is provided by NIH grant P30 DC04665.

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