Apoptosis in cavitation of middle ear space

Abstract

Mesenchyme cells surround early ossicles in the developing middle ear, then are replaced by space that is created by what has been described as an expansion of the pharyngeal pouch. Cell death has not been considered important in cavitation of chick middle ear (Jaskoll and Maderson [1978] Anat. Rec., 190:177-200), but an uncharacterized form of cell death has been reported to play a major role in cavitation of mouse middle ear (Jaskoll [1977] PhD thesis, CUNY). We investigated whether this uncharacterized cell death is the non-random form known as apoptosis. We examined the middle ear cavitation process using an in situ immunomarker for apoptosis. CBy RF mice during prenatal days 15-20 and postnatal days 1-3 and chick embryos representing HH stages 33-38 were investigated. Apoptotic cells were marked in mouse postnatal day 1. No indication of apoptosis was present in other prenatal and postnatal days of development included in this study, although morphology showed that cavitation proceeds over several perinatal days in the mouse. Apoptosis was not marked in the chick middle ear. Previously observed cell death in murine middle ear is the non-random form of cell death known as apoptosis. Cell death has not been reported in avian middle ear, and lack of apoptotic marker supports those observations. The limited occurrence of apoptosis in mice and apparent absence of apoptosis in chicks suggest that several mechanisms contribute to cavitation of vertebrate middle ear space.

Eya4-deficient mice are a model for heritable otitis media

“…Before day 6, the external earflap (pinna) was folded in both wild-type and Eya4 -/-mice, providing a protective barrier, and the middle ear cavity was filled with mesenchymal cells, as has been previously reported (23). There was no delay in the onset of middle ear cavitation (24), which became evident at day 6, and no inflammation in the newly formed small middle ear space in wild-type or Eya4 -/-mice ( Figure 3A). At days 11-12, when the pinna was unfolded in all mice, the middle ear cavity was largely aerated and mesenchymal cells were found only near ossicles in wild-type mice.…”

The development of the mammalian outer and middle ear

“…Further evidence to support this comes from work in the opossum and in humans where the volume of mesenchyme within the middle ear at various times was calculated and found to remain the same (Piza et al 1998). Additionally, no extensive apoptosis has ever been detected within the middle ear mesenchyme that would explain the clearance (Roberts & Miller, 1998). The dual origin of the middle ear epithelium is unique to mammals, and the development of the threeossicle mammalian middle ear may have lead to its evolution (Thompson & Tucker, 2013).…”