Mitotic and Nonmitotic Hair Cell Regeneration in the Bullfrog Vestibular Otolith Organs<sup>a</sup>

Baird, Richard A.; Steyger, Peter S.; Schuff, N. R.

doi:10.1111/j.1749-6632.1996.tb15693.x

Cited by 120 publications

(129 citation statements)

References 39 publications

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“…In vivo, GTTR uptake was more prominent in mature hair cells, mirroring the pattern of more rapid aminoglycoside-induced cell death by mature hair cells compared to immature hair cells (Baird et al, 1996). The weaker uptake of GTTR in many peripheral, immature hair cells in vivo may also account for enhanced resistance of regenerating/immature hair cells to aminoglycoside toxicity (Baird et al, 1996;Hashino and Salvi, 1996).…”

Section: Bullfrog Sacculementioning

confidence: 90%

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

et al. 2006

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Aminoglycoside uptake in the inner ear remains poorly understood. We subcutaneously injected a fluorescently-conjugated aminoglycoside, gentamicin-Texas Red (GTTR), to investigate the in vivo uptake of GTTR in the inner ear of several vertebrates, and in various murine sensory cells using confocal microscopy.In bullfrogs, GTTR uptake was prominent in mature hair cells, but not in immature hair cells. Avian hair cells accrued GTTR more rapidly at the base of the basilar papilla. GTTR was associated with the hair bundle; and, in guinea pigs and mice, somatic GTTR fluorescence was initially diffuse before punctate (endosomal) fluorescence could be observed. A baso-apical gradient of intracellular GTTR uptake in guinea pig cochleae could only be detected at early time points (<3 h). In 21−28 day mice, cochlear GTTR uptake was greatly reduced compared to guinea pigs, 6-day-old mice, or mice treated with ethacrynic acid. In mice, GTTR was also rapidly taken up, and retained, in the kidney, dorsal root and trigeminal ganglia. In linguinal and vibrissal tissues rapid GTTR uptake cleared over a period of several days.The preferential uptake of GTTR by mature saccular, and proximal hair cells resembles the pattern of aminoglycoside-induced hair cell death in bullfrogs and chicks. Differences in the degree of GTTR uptake in hair cells of different species suggests variation in serum levels, clearance rates from serum, and/or the developmental and functional integrity of the blood-labyrinth barrier. GTTR uptake by hair cells in vivo suggests that GTTR has potential to elucidate aminoglycoside transport mechanisms into the inner ear, and as a bio-tracer for in vivo pharmacokinetic studies.

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Section: Bullfrog Sacculementioning

confidence: 90%

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

et al. 2006

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“…These observations suggest many HCs were regenerated by direct transdifferentiation, during which an SC converts phenotypically into an HC without dividing. Further evidence for this phenomenon, which was proposed in the mid-1990s (Baird et al 1996;Adler and Raphael 1996;Roberson et al 1996), was recently provided by the observation that SCs upregulate the HC-specific protein Atoh1 shortly after HC damage is initiated in chickens in vivo (Cafaro et al 2007). We provide additional evidence for "transitional" cells here.…”

Section: Hair Cells Are Regenerated By Mitotic and Nonmitotic Meansmentioning

confidence: 94%

“…Aphidicolin blocks a wide range of cell types from progressing past the G1/S border of the cell cycle (Pedrali-Noy et al, 1980). At 25 µM, aphidicolin has also been shown to block SC division in newt saccules (Taylor and Forge 2005) and frog saccules (Baird et al 1996(Baird et al , 2000Gale et al 2002).…”

Section: Supporting Cell Division Is Drastically Inhibited With Aphidmentioning

confidence: 99%

“…This process contributes to HC regeneration in cultured saccules of frogs and salamanders after aminoglycoside-induced injury (Baird et al 1996(Baird et al , 2000Taylor and Forge 2005). In chickens, some regenerated auditory HCs are unlabeled for a proliferation marker ( 3 H-thymidine or bromodeoxyuridine (BrdU)) despite its continual perfusion into the inner ear after damage (Roberson et al 1996(Roberson et al , 2004.…”

Section: Introductionmentioning

confidence: 99%

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Supporting Cell Division Is Not Required for Regeneration of Auditory Hair Cells After Ototoxic Injury In Vitro

Shang

Cafaro

Nehmer

et al. 2010

JARO

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In chickens, nonsensory supporting cells divide and regenerate auditory hair cells after injury. Anatomical evidence suggests that supporting cells can also transdifferentiate into hair cells without dividing. In this study, we characterized an organ culture model to study auditory hair cell regeneration, and we used these cultures to test if direct transdifferentiation alone can lead to significant hair cell regeneration. Control cultures (organs from posthatch chickens maintained without streptomycin) showed complete hair cell loss in the proximal (high-frequency) region by 5 days. In contrast, a 2-day treatment with streptomycin induced loss of hair cells from all regions by 3 days. Hair cell regeneration proceeded in culture, with the time course of supporting cell division and hair cell differentiation generally resembling in vivo patterns. The degree of supporting cell division depended upon the presence of streptomycin, the epithelial region, the type of culture media, and serum concentration. On average, 87% of the regenerated hair cells lacked the cell division marker BrdU despite its continuous presence, suggesting that most hair cells were regenerated via direct transdifferentiation. Addition of the DNA polymerase inhibitor aphidicolin to culture media prevented supporting cell division, but numerous hair cells were regenerated nonetheless. These hair cells showed signs of functional maturation, including stereociliary bundles and rapid uptake of FM1-43. These observations demonstrate that direct transdifferentiation is a significant mechanism of hair cell regeneration in the chicken auditory after streptomycin damage in vitro.

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“…As HCs are lost, function deteriorates. Nonmammalian vertebrates are able to replace the lost HCs via two processes: the cell division of resident progenitor/stem cells and the direct conversion of another cell type (e.g., support cells [SCs]) into HCs without an intervening mitosis (Corwin and Cotanche 1988;Ryals and Rubel 1988;Adler and Raphael 1996;Baird et al 1996;Roberson et al 1996Roberson et al , 2004Taylor and Forge 2005). Humans and other mammals, in contrast, are unable to replace lost auditory HCs and have limited ability to regenerate vestibular HCs (reviewed in Bermingham-McDonogh and Rubel 2003;Oesterle and Stone 2008).…”

Section: Introductionmentioning

confidence: 99%

Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear

Oesterle

Campbell

Taylor³

et al. 2007

JARO

212

245

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Inner ear hair cells detect environmental signals associated with hearing, balance, and body orientation. In humans and other mammals, significant hair cell loss leads to irreversible hearing and balance deficits, whereas hair cell loss in nonmammalian vertebrates is repaired by the spontaneous generation of replacement hair cells. Research in mammalian hair cell regeneration is hampered by the lack of in vivo damage models for the adult mouse inner ear and the paucity of cell-type-specific markers for nonsensory cells within the sensory receptor epithelia. The present study delineates a protocol to drug damage the adult mouse auditory epithelium (organ of Corti) in situ and uses this protocol to investigate Sox2 and Jagged1 expression in damaged inner ear sensory epithelia. In other tissues, the transcription factor Sox2 and a ligand member of the Notch signaling pathway, Jagged1, are involved in regenerative processes. Both are involved in early inner ear development and are expressed in developing support cells, but little is known about their expressions in the adult. We describe a nonsurgical technique for inducing hair cell damage in adult mouse organ of Corti by a single high-dose injection of the aminoglycoside kanamycin followed by a single injection of the loop diuretic furosemide. This drug combination causes the rapid death of outer hair cells throughout the cochlea. Using immunocytochemical techniques, Sox2 is shown to be expressed specifically in support cells in normal adult mouse inner ear and is not affected by drug damage. Sox2 is absent from auditory hair cells, but is expressed in a subset of vestibular hair cells. Double-labeling experiments with Sox2 and calbindin suggest Sox2-positive hair cells are Type II. Jagged1 is also expressed in support cells in the adult ear and is not affected by drug damage. Sox2 and Jagged1 may be involved in the maintenance of support cells in adult mouse inner ear.

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Mitotic and Nonmitotic Hair Cell Regeneration in the Bullfrog Vestibular Otolith Organs^a

Cited by 120 publications

References 39 publications

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

Supporting Cell Division Is Not Required for Regeneration of Auditory Hair Cells After Ototoxic Injury In Vitro

Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear

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Mitotic and Nonmitotic Hair Cell Regeneration in the Bullfrog Vestibular Otolith Organsa

Cited by 120 publications

References 39 publications

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

Supporting Cell Division Is Not Required for Regeneration of Auditory Hair Cells After Ototoxic Injury In Vitro

Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear

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Mitotic and Nonmitotic Hair Cell Regeneration in the Bullfrog Vestibular Otolith Organs^a