Continuous Hair Cell Turnover in the Inner Ear Vestibular Organs of a Mammal, the Daubenton's Bat ( Myotis daubentonii )

Kirkegaard, Mette; Jørgensen, J. Mørup

doi:10.1007/s001140050015

Cited by 27 publications

(21 citation statements)

References 19 publications

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“…A diagram of this cell (L) also shows a GFP + nonsensory cell and two GFP + support cells surrounding the hair cell. Steyger et al 1997), chicks (Raphael et al 1994Adler and Raphael 1996;Adler et al 1997), bats (Kirkegaard andJorgensen 2000), and guinea pigs (Li and Forge 1997). Since hair cell regeneration occurs in most vertebrate species, it is perhaps unsurprising that these different species show similar changes as cells transition between the distinct morphologies of support cells and hair cells.…”

Section: Fig 8 Examples Of Lineage Traced Transitional Cells (Tc) mentioning

confidence: 99%

Hair Cell Generation by Notch Inhibition in the Adult Mammalian Cristae

Slowik

Bermingham‐McDonogh

2013

JARO

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Balance disorders caused by hair cell loss in the sensory organs of the vestibular system pose a significant health problem worldwide, particularly in the elderly. Currently, this hair cell loss is permanent as there is no effective treatment. This is in stark contrast to nonmammalian vertebrates who robustly regenerate hair cells after damage. This disparity in regenerative potential highlights the need for further manipulation in order to stimulate more robust hair cell regeneration in mammals. In the utricle, Notch signaling is required for maintaining the striolar support cell phenotype into the second postnatal week. Notch signaling has further been implicated in hair cell regeneration after damage in the mature utricle. Here, we investigate the role of Notch signaling in the mature mammalian cristae in order to characterize the Notch-mediated regenerative potential of these sensory organs. For these studies, we used the γ-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-Lalanyl]-S-phenylglycine t-butyl ester (DAPT), in conjunction with a method we developed to culture cristae in vitro. In postnatal and adult cristae, we found that 5 days of DAPT treatment resulted in a downregulation of the Notch effectors Hes1 and Hes5 and also an increase in the total number of Gfi1 + hair cells. Hes5, as reported by Hes5-GFP, was downregulated specifically in peripheral support cells. Using lineage tracing with proteolipid protein (PLP)/CreER;mTmG mice, we found that these hair cells arose through transdifferentiation of support cells in cristae explanted from mice up to 10 weeks of age. These transdifferentiated cells arose without proliferation and were capable of taking on a hair cell morphology, migrating to the correct cell layer, and assembling what appears to be a stereocilia bundle with a long kinocilium. Overall, these data show that Notch signaling is active in the mature cristae and suggest that it may be important in maintaining the support cell fate in a subset of peripheral support cells.

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Section: Fig 8 Examples Of Lineage Traced Transitional Cells (Tc) mentioning

confidence: 99%

Hair Cell Generation by Notch Inhibition in the Adult Mammalian Cristae

Slowik

Bermingham‐McDonogh

2013

JARO

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“…Small HCs have been described in the inner ear vestibular sensory epithelia of all vertebrates examined (Jørgensen 1970(Jørgensen , 1975Li 1973, 1975;Corwin 1983;Mathiesen 1985;Rubel et al 1995;Kirkegaard and Jørgensen 2000). It has also been observed that the stereovilli of small HCs are thinner than stereovilli on normal-sized HCs (Jørgensen 1970(Jørgensen , 1975Mathiesen 1985;Kirkegaard and Jørgen-sen 2000).…”

Section: Formation Of New Hcs In the Ummentioning

confidence: 99%

“…Details concerning the architectural mechanisms which govern the apical development of small HCs with thin stereovilli have been given by Tilney et al (1992). Furthermore, a TEM study on Daubenton's bat Myotis daubentonii has revealed that the small HCs are basally innervated (Kirkegaard and Jørgensen 2000). These observations, together with the fact that apoptotic HCs have been observed in representatives of all other vertebrate classes (Jørgensen 1981;Jørgensen and Mathiesen 1988;Jørgensen and Locket 1995;Kirkegaard and Jørgen-sen 2000;Jensen and Jørgensen 2001), strongly indicate that small HCs are early stages of functionally mature ones.…”

Section: Formation Of New Hcs In the Ummentioning

confidence: 99%

Structure and Growth of the Utricular Macula in the Inner Ear of the Slider Turtle Trachemys scripta

Severinsen

Jørgensen²,

Nyengaard

2003

JARO - Journal of the Association for Research in Otolaryngolog

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In general, postembryonic production of inner ear vestibular hair cells (HCs) is believed to occur in all nonmammalian vertebrates. However, no study on this topic has been published on reptiles and, consequently, it is not known whether this also applies to these vertebrates. Therefore, the present study applied stereological methods in order to estimate the total number of HCs in turtles of varying sizes. The findings are that in prehatchlings the utricular macula (UM) contains~4000 HCs as compared to~5000 in juveniles,~8000 in medium-sized turtles, and 12,000 in large, sexually mature turtles. Scanning electron microscopy (SEM) reveals that presumably newly generated HCs with small surface areas and thin stereovilli are found in all regions of the UM. Furthermore, it reveals that utricular HCs can be classified as belonging to a specific region from the morphology of their apical structure. Striolar HCs have a large free oval-to-ovoid surface, a hair bundle with numerous stereovilli, and a short kinocilium. Rampary and cotillary HCs have smaller and slimmer free surfaces, comparatively fewer stereovilli, but much longer kinocilia. In conclusion, the current study demonstrates that postembryonic production of HCs does occur in reptiles and thereby supports the general view that this is a common trait in all nonmammalian vertebrates.

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“…For example, studies suggest that bats may be able to generate new hair cells within certain regions of the inner ear after birth (Kirkegaard and Jørgensen 2000); although the functional impact of this on their sensory perception remains unclear. The particular diets of bat species may be either high in fats or sugars, yet bats appear to avoid the associated health implications such as artherosclerosis or hyperglycemia (Widmaier et al, 1996;Brunet-Rossinni and Austad 2004;Mqokeli and Downs 2012) which are frequently seen in ageing human populations.…”

Section: Introductionmentioning

confidence: 99%

Molecular evolution of growth hormone and insulin-like growth factor 1 receptors in long-lived, small-bodied mammals

Davies

Tsagkogeorga

Bennett

et al. 2014

Gene

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Mammals typically display a robust positive relationship between lifespan and body size.Two groups that deviate markedly from this pattern are bats and the African mole-rats; with members of both groups being extremely long-lived given their body size, with the maximum documented lifespan for many species exceeding 20 years. A recent genomics study of the exceptionally long-lived Brandt's bat, Myotis brandtii (41 years), suggested its longevity and small body size may be at least partly attributed to key amino acid substitutions in the transmembrane domains of the receptors of growth hormone (GH) and insulin-like growth factor 1 (IGF1). However, whereas elevated longevity is likely to be common across all 19 bat families, the reported amino acid substitutions were only observed in two closely related bat families. To test the hypothesis that an altered GH/IGF1 axis relates to the longevity of African mole-rats and bats, we compared and analysed the homologous coding gene sequences in genomic and transcriptomic data from 26 bat species, five mole-rats and 38 outgroup species. Phylogenetic analyses of both genes recovered the majority of nodes in the currently accepted species tree with high support. Compared to other clades, such as primates and carnivores, the bats and rodents had longer branch lengths. The single 24 amino acid transmembrane domain of IGF1R was found to be more conserved across mammals compared to that of GHR.Within bats, considerable variation in the transmembrane domain of GHR was found, including a previously unreported deletion within the Emballonuridae. The transmembrane domains of rodents were found to be more conserved, with mole-rats lacking uniquely conserved amino acid substitutions. Molecular evolutionary analyses showed that both genes were under purifying selection in bats and mole-rats. Our findings suggest that while the previously documented mutations may confer some additional lifespan to Myotis bats, other, as yet unknown, genetic differences are likely to account for the long lifespans observed in many bat and mole-rat species.

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Continuous Hair Cell Turnover in the Inner Ear Vestibular Organs of a Mammal, the Daubenton's Bat ( Myotis daubentonii )

Cited by 27 publications

References 19 publications

Hair Cell Generation by Notch Inhibition in the Adult Mammalian Cristae

Hair Cell Generation by Notch Inhibition in the Adult Mammalian Cristae

Structure and Growth of the Utricular Macula in the Inner Ear of the Slider Turtle Trachemys scripta

Molecular evolution of growth hormone and insulin-like growth factor 1 receptors in long-lived, small-bodied mammals

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