Development and self-repair in hair cell epithelia

This presentation will attempt to explain current understanding of the cellular mechanisms of normal hair cell development and the mechanisms of hair cell regeneration. Hair cells are the mechanoreceptors that transduce sound and balance stimulation of the ear and water current stimulation of the lateral line organs into electrical activity that is transmitted to the brain. Hair cells have one true cilium, the kinocilium, and 30 to 200 or more stereocilia which are modified, actin-filled microvilli, that project from the flat apical surfaces of the cells. The stereocilia are arrayed across each cell in an “organ pipe” arrangement, with a row of short stereocilia at one end and rows of increasingly taller stereocilia proceeding from that row toward the single eccentrically positioned kinocilium. That asymmetrical surface structure defines the functional polarity of each hair cell, because stimuli that mechanically bend the stereocilia array in the direction of its tall end cause a decrease in the transmembrane potential of the hair cell and increased exocytotic release of neurotransmitter from vesicles at tonically active synaptic sites in the subnuclear region. In that way the appropriately directed bending of the stereocilia causes excitation of neurons that conduct action potentials to the brain. Bending of the stereocilia in the opposite direction causes hyperpolarization of the hair cell, reduction in the exocytosis of neurotransmitter, and a resulting decrease in the frequency of action potentials conducted to the brain. In most mature organs the orientations of the stereocilia arrays of the hair cells are aligned throughout the epithelia. However, during early development of these cells their cilia bundles are oriented in a nearly random distribution. As the cells differentiate their cilia arrays grow taller and reorient, so that neighbors come into alignment. In some epithelia, such as the auditory epithelium in the cochlea of the chicken, both the number and the maximum length of the stereocilia on hair cells vary systematically along gradients related to cell position in the epithelium. This pattern of sensory cell ultrastructure correlates with the high to low pitch tuning of the basilar membrane that supports the epithelium and with the tuning of the neurons that contact the individual cells. Cells at the distal end of the chicken cochlea have less than 50 stereocilia; cells at the proximal end have over 200. The stereocilia on proximal hair cells are short (<2 microns); those on distal hair cells are long (>5 microns). The reorientation of the stereocilia arrays and their location-specific differences in stereocilia number and length all become recognizable at approximately the time when synapses form between these cells and their neurons, but experiments have shown that these processes of hair cell differentiation can occur in the absence of neurons. Several hypotheses that attempt to explain the control of differentiation in hair cells will be covered