Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

Abstract

Hair cells in many nonmammalian vertebrates are regenerated by the mitotic division of supporting cell progenitors and the differentiation of the resulting progeny into new hair cells and supporting cells. Recent studies have shown that nonmitotic hair cell recovery after aminoglycoside-induced damage can also occur in the vestibular organs. Using hair cell and supporting cell immunocytochemical markers, we have used confocal and electron microscopy to examine the fate of damaged hair cells and the origin of immature hair cells after gentamicin treatment in mitotically blocked cultures of the bullfrog saccule. Extruding and fragmenting hair cells, which undergo apoptotic cell death, are replaced by scar formations. After losing their bundles, sublethally damaged hair cells remain in the sensory epithelium for prolonged periods, acquiring supporting cell-like morphology and immunoreactivity. These modes of damage appear to be mutually exclusive, implying that sublethally damaged hair cells repair their bundles. Transitional cells, coexpressing hair cell and supporting cell markers, are seen near scar formations created by the expansion of neighboring supporting cells. Most of these cells have morphology and immunoreactivity similar to that of sublethally damaged hair cells. Ultrastructural analysis also reveals that most immature hair cells had autophagic vacuoles, implying that they originated from damaged hair cells rather than supporting cells. Some transitional cells are supporting cells participating in scar formations. Supporting cells also decrease in number during hair cell recovery, supporting the conclusion that some supporting cells undergo phenotypic conversion into hair cells without an intervening mitotic event.

Posture, Head Stability, and Orientation Recovery During Vestibular Regeneration In Pigeons

“…In the utricle, systemic injections typically damaged on even smaller percentage of cells (Lindeman 1969;Matsui et al 2003;Weisleder and Rubel 1993;Wersäll and Hawkins 1962). Thus, the observed recoveries in chicks were likely not due to regeneration alone but were coupled with possible remaining function of nondamaged hair cells as well as the rescue and repair of sublethally damaged hair cells (Baird et al 2002). Second, the previous regenerative investigations of VOR and VCR recovery were performed in young hatchling chicks compared with adult pigeons in the current report.…”

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

“…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).…”

“…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.…”

Development of the zebrafish inner ear

“…Hair cell death then disrupts the feedback signal and triggers changes in one or more adjacent supporting cells, leading to a regenerative response. In all vertebrates (although not in the mammalian cochlea), hair cell regeneration can occur by either of two mechanisms (Baird et al, 2000;Stone and Rubel, 2000): Supporting cells can directly trans-differentiate into hair cells with no intervening cell division or can undergo asymmetric cell division to generate hair cells and new supporting cells. Supporting cells can also divide symmetrically to yield two new supporting cells.…”