33 research outputs found

    Developmental segregation in the afferent projections to mammalian auditory hair cells.

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    Hes5 Expression in the Postnatal and Adult Mouse Inner Ear and the Drug-Damaged Cochlea

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    The Notch signaling pathway is known to have multiple roles during development of the inner ear. Notch signaling activates transcription of Hes5, a homologue of Drosophila hairy and enhancer of split, which encodes a basic helix-loop-helix transcriptional repressor. Previous studies have shown that Hes5 is expressed in the cochlea during embryonic development, and loss of Hes5 leads to overproduction of auditory and vestibular hair cells. However, due to technical limitations and inconsistency between previous reports, the precise spatial and temporal pattern of Hes5 expression in the postnatal and adult inner ear has remained unclear. In this study, we use Hes5-GFP transgenic mice and in situ hybridization to report the expression pattern of Hes5 in the inner ear. We find that Hes5 is expressed in the developing auditory epithelium of the cochlea beginning at embryonic day 14.5 (E14.5), becomes restricted to a particular subset of cochlear supporting cells, is downregulated in the postnatal cochlea, and is not present in adults. In the vestibular system, we detect Hes5 in developing supporting cells as early as E12.5 and find that Hes5 expression is maintained in some adult vestibular supporting cells. In order to determine the effect of hair cell damage on Notch signaling in the cochlea, we damaged cochlear hair cells of adult Hes5-GFP mice in vivo using injection of kanamycin and furosemide. Although outer hair cells were killed in treated animals and supporting cells were still present after damage, supporting cells did not upregulate Hes5-GFP in the damaged cochlea. Therefore, absence of Notch-Hes5 signaling in the normal and damaged adult cochlea is correlated with lack of regeneration potential, while its presence in the neonatal cochlea and adult vestibular epithelia is associated with greater capacity for plasticity or regeneration in these tissues; which suggests that this pathway may be involved in regulating regenerative potential

    Passive basilar membrane vibrations in gerbil neonates: mechanical bases of cochlear maturation

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    Using a laser velocimeter, basilar membrane (BM) responses to tones were measured in neonatal gerbils at a site near the round window of the cochlea. In adult gerbils, ‘active’ BM responses at this site are most sensitive at 34–37 kHz and exhibit a compressive non-linearity. Postmortem, BM responses in adults become ‘passive’, i.e. linear and insensitive, and the best frequency (BF) shifts downwards by about 0.5 octaves. At 14 and 16 days after birth (DAB), BM responses in neonatal gerbils were passive but otherwise very different from postmortem responses in adult gerbils: BF was more than an octave lower, the steep slopes of the phase vs. frequency curves were shifted downwards in frequency by nearly 1 octave, and the maximum phase lags amounted to only 180 deg relative to stapes. BFs and phase lags increased systematically between 14 and 20 DAB, implying drastic alterations of the passive material properties of cochlear tissues and accounting for a large part of the shift in BF that characterizes maturation of auditory nerve responses during the same period
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