Abstract
BackgroundThe greater epithelial ridge (GER) is a developmental structure in the maturation of the organ of Corti. Situated near the inner hair cells of neonatal mice, the GER undergoes a wave of apoptosis after postnatal day 8 (P8). We evaluated the GER from P8 to P12 in transgenic mice that carry the R75W + mutation, a dominant-negative mutation of human gap junction protein, beta 2, 26 kDa (GJB2) (also known as connexin 26 or CX26). Cx26 facilitate intercellular communication within the mammalian auditory organ.ResultsIn both non-transgenic (non-Tg) and R75W + mice, some GER cells exhibited apoptotic characteristics at P8. In the GER of non-Tg mice, both the total number of cells and the number of apoptotic cells decreased from P8 to P12. In contrast, apoptotic cells were still clearly evident in the GER of R75W + mice at P12. In R75W + mice, therefore, apoptosis in the GER persisted until a later stage of cochlear development. In addition, the GER of R75W + mice exhibited morphological signs of retention, which may have resulted from diminished levels of apoptosis and/or promotion of cell proliferation during embryogenesis and early postnatal stages of development.ConclusionsHere we demonstrate that Cx26 dysfunction is associated with delayed apoptosis of GER cells and GER retention. This is the first demonstration that Cx26 may regulate cell proliferation and apoptosis during development of the cochlea.
Highlights
The greater epithelial ridge (GER) is a developmental structure in the maturation of the organ of Corti
We have demonstrated that a dominant-negative GJB2 mutation results in incomplete postnatal development of the cochlear organ of Corti by R75W + transgenic mice, which carry a dominant-negative mutation of human connexin 26 (CX26) [6,7]
Programmed cell death with Caspase-3 activation in GER To investigate whether the programmed cell death in GER of R75W + mice was affected, we performed whole mount immunostaining of the cochlea with anti-Cleaved Caspase-3 (C-Casp3) antibody
Summary
The greater epithelial ridge (GER) is a developmental structure in the maturation of the organ of Corti. We evaluated the GER from P8 to P12 in transgenic mice that carry the R75W + mutation, a dominant-negative mutation of human gap junction protein, beta 2, 26 kDa (GJB2) ( known as connexin 26 or CX26). We have demonstrated that a dominant-negative GJB2 mutation results in incomplete postnatal development of the cochlear organ of Corti by R75W + transgenic mice, which carry a dominant-negative mutation of human CX26 [6,7]. The greater epithelial ridge (GER) is a developmental structure that is important during maturation of the organ of Corti in mice. We have shown that development of normal hearing function in C3H/HeJ mice requires a wave of programmed cell death in the GER from P7 to P12. We observed mitosis in the GER after P7, indicating that GER cells are both degenerating and regenerating until their eventual elimination at P12 [13]
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