Hollyfield: Regulator of inner ear progenitor fate and outer hair cell function.
Located within the mammalian cochlea and critical to hearing function, the organ of Corti is a sensory epithelium, comprised of auditory receptors, called hair cells, and their supporting cells. In avians, hair cells and supporting cells share common progenitors in the auditory epithelia (Fekete et al., 1998; Kirjavainen et al., 2008). During embryonic development it is crucial to have the right number of hair cells and supporting cells from progenitor cells for proper organ function. Loss or even gain of supernumerary hair cells and/or supporting cells can lead to deafness (Chen et al., ...view middle of the document...
The arrangement of IHCs and OHCs is important for micromechanics involved in sensory transduction (Lim, 1986). IHCs are located close to the osseous spiral lamina, of which the motion of the basiliar membrane is minimal, whereas, OHCs are located on the basiliar membrane where there is greater motion (Lim, 1986). Not only can the loss of inner hair cells lead to deafness, but so can the loss of outer hair cells. In rats, loss of 1/3 of OHCs will cause hearing impairment, and 2/3 loss will lead to deafness (Chen et al., 2008) .
Supporting cells: Within the organ of Corti, there are also five different types of supporting cells with distinct morphologies: Hensen’s cells are cuboidal or slightly oblong, inner phalangeal cells and border cells are columnar, and Deiters’ and pillar cells are elongated and have strong cytoskeletons for large structural demands (Wan et al., 2013). Like hair cells, supporting cells are also precisely arranged in the organ of Corti, by rows from the outer edge to the inner edge of the organ in the order of: Hensen’s cells, Deiters’ cells, pillar cells, inner phalangeal cells, and border cells (Wan et al., 2013). One should note that supporting cells do not just take up space in the auditory epithelium. Loss of Deiters’ and pillar cells enviably leads to a loss of OHCs, causing deafness due lack of amplification (Mellado Lagarde et al., 2013). In addition, supporting cells also provide trophic factors, which are vital to the maintenance of spiral ganglion neurons (Monzack and Cunningham, 2013)
Cell cycle exit and p27kip1
To get the right number of hair cells and supporting cells during development, cell cycle exit in the organ of Corti needs to be properly timed (Chen and Segil, 1999; Lee et al., 2006). Regulation of cell division during embryonic cochlear development of the prosensory domain is correlated with p27kip1 expression (Lee et al., 2006). In wildtype (WT) mice, cell cycle exit in the developing organ of Corti starts at approximately E12.5 and proceeds in a wave marked by p27kip1 expression from apex to base of the cochlea, until around E14.5 (Lee et al., 2006). The wave of cell cycle exit marked by p27kip1, creates a zone of non-proliferating cells, so that hair cell differentiation can take place (Lee et al., 2006). In p27kip1-/- mice, cell cycle exit is delayed to approximately E14.5 and follows instead the wave of hair cell differentiation from base to apex (Lee et al., 2006). The delay in cell cycle exit causes the formation of supernumerary hair cells and supporting cells (Chen and Segil, 1999). Cell cycle exit needs to be precisely timed to govern the correct number of progenitor cells, which will give rise to hair cells and supporting cells in the developing organ of Corti (Lee et al., 2006) .
Differentiation of hair cells and supporting cells
Hair cells: Once cell cycle exits are completed, progenitor cells can undergo differentiation to become the diverse cell types that make up the organ of Corti....