Apoptosis in the developing rat cochlea and its related structures

Mammalian development involves proliferation and programmed cell death (apoptosis). This study was undertaken to analyse the spatial and temporal organisation of apoptosis in developing rat cochlear and associated tissues using in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling of DNA fragments (TUNEL), and light and electron microscopy. Embryonic (E12-E19 days) and postnatal rats (P0-P21 days) were studied. Fixed tissues were stained for apoptosis using TUNEL technique and the cytomorphology of apoptosis was confirmed by light and electron microscopy. Apoptotic cells were detected predominantly during the embryonic and early postnatal development of the cochlea. Apoptosis occurred in embryonic precursors of the cochlear duct epithelium, mainly in the region of its outgrowth between E12 and E16. In the periotic mesenchyme, apoptosis occurred in areas committed to develop into the middle ear cavity (peaking at E16) and perilymphatic compartments (peaking around E18-E19). Apoptosis in the VIIIth nerve (statoacoustic) ganglion was detected throughout the embryonic and early postnatal periods, peaking at E18-E19, around the time when the cochlear neural connections are being established. At later postnatal days, apoptosis was seen only occasionally in cochlear tissues, predominantly in tissues lining the middle ear cavity and sporadically in cells of the otic capsule. Therefore, apoptosis appears to occur in areas of remodeling, in areas of cavitation and in areas of differentiation. These findings provide a template for studying the molecular mechanisms involved in the development of the rat inner ear.