EARLY INNERVATION AND DIFFERENTIATION OF CELLS IN THE HUMAN ORGAN OF CORTI.

OBJECTIVE: Knowledge on spatio-temporal interplay of factors controlling differentiation and innervation of cochlear cells in human inner ear is essential for understanding of normal hearing function. Similar studies on the early human inner ear are missing. MATERIALS and METHODS: The immunolocalization of different factors controlling apoptosis (caspase-3), innervation (PGP9.5), differentiation (nestin) and cilia detection (a-tubuline) in cochlear cells was histologically analyzed in 6 human conceptuses, 5th to 10th weeks-old. RESULTS: During the analyzed developmental period, otocyst epithelium displayed initial differentiation into the cell of organ of Corti. Throughout the investigated period, apoptotic caspase-3 positive cells were mainly distributed at the luminal and basal surfaces of labyrinth epithelium. Apoptosis co-localized with entrance of nerve fibers (visualized by PGP 9.5) into the basal parts of sensorineural cochlear epithelium. Expression of intermediate filament nestin characterized basal parts of cochlear cells, nerve fibers and cochlear ganglion cells. Protein a-tubuline was first detected in primary cilia of both epithelial and mesenchymal cells in the labyrinth, while later on characterized stereocilia on the surfaces of hair cells. Conclusion The described expression pattern indicates importance of early innervation of otocyst for differentiation of specific cells within the organ of Corti. Basal apoptosis seems to be associated with cochlear innervation, while luminal apoptosis with selective thinning of the cochlear epithelial wall. Expression of nestin and primary cilia characterized immature cochlear cells, while appearance of stereocilia characterized differentiation of hair cells. Alterations in spatiotemporal interplay of investigated developmental factors might lead to disturbances in cochlear cells morphogenesis and hearing function. [ABSTRACT FROM AUTHOR]