Evidence for a partial epithelial-mesenchymal transition in rat auditory organ development

An epithelial-mesenchymal transition is a biological process that allows a polarized epithelial cell to undergo multiple biochemical changes that enable it to assume a mesenchymal cell phenotype. During this process, epithelial cells loosen cell-cell adhesion, module their polarity and rearrange their cytoskeleton: intermediate filaments typically switch from cytokeratin to vimentin. They also enhance their motility capacity. The epithelial-mesenchymal transition plays key roles in the formation of the body plan and in the differentiation of multiple tissues and organs but it is also involved in tissue repair, tissue homeostasis, fibrosis, and carcinoma progression.
Until now, epithelial-mesenchymal transition has been rarely mentioned in the inner ear organogenesis. In chick, epithelial-mesenchymal transition has been reported as a possible mechanism of semicircular canal morphogenesis. More recently, an in vitro study has also indicated that sensory epithelial cells from mouse utricle can undergo an epithelial-mesenchymal transition to become cells expressing features of prosensory cells. By contrast, epithelial-mesenchymal transition has never been observed during auditory organ morphogenesis.
The auditory organ, the organ of Corti, is a highly specialized structure composed by specific cellular types. The sensory cells are characterized by stereocilia at their apex and are necessary for the sound perception. Theses cells are supported by supporting cells. Based on their morphology and physiology, at least four types of supporting cells can be identified in the organ of Corti: inner and outer pillar cells, phalangeal cell and Deiter’s cells. The inner pillar cells and outer pillar cells combine to form the tunnel of Corti, a fluid filled triangular space that separates the single row of inner hair cells from the first row of outer hair cells. The Nuel spaces are another interval in the organ of Corti that is situated between the outer pillar cells and the different rows of outer hair cells and Deiters cells.

To determine whether an epithelial-mesenchymal transition may play a role in the morphogenesis of the auditory organ, we studied the spatial localization of several epithelial-mesenchymal transition markers, the cell-cell adhesion molecules and intermediate filament cytoskeletal proteins, in epithelium of the dorsal cochlea during development of the rat organ of Corti from 18th embryonic day until 25th postnatal day.
We examined by confocal microscopy immunolabelings on cryosections of whole cochleae with antibodies anti-cytokeratins as well as with antibodies anti-vimentin, anti-E-cadherin and anti-beta-catenin.Our results showed a partial loss of E-cadherin and beta-catenin between supporting cells at P8 and P12, respectively, and a temporary appearance of vimentin in pillar cells and Deiters between P8 and P10.

Our results show a local loss of adhesion between supporting cells of the OC from P8, an increase expression of cytokeratins in supporting cells around P10 and a temporary appearance of vimentin in supporting cells at P8-10. These observations suggest that a partial epithelial-mesenchymal transition might be involved in the remodeling of the Corti organ during the postnatal stages of development in rat.