A recent study analyzing gene expression in the inner ear of the chicken may provide new insights into the root causes of hearing and balance disorders in humans.

The organs of the inner ear serve two vital roles—hearing and the maintenance of balance—both mediated through the actions of specialized epithelia known as hair cells. In the utricle, movement results in the shifting of fluids, triggering the motion-specific activation of hair cells, which then transmit information regarding the orientation of the body. In the cochlea, sound waves trigger the vibration of membranes, resulting in the deformation of patches of hair cells and the transmission of auditory signals.

Most vertebrates can regenerate damaged hair cells, maintaining epithelial supporting cells in the inner ear as precursors to new hair cells. Unfortunately, mammals have lost this ability, and hair cell damage ultimately results in deafness or balance-related disorders.

“Mammals have these epithelial supporting cells,” explains Michael Lovett, a researcher at Washington University School of Medicine (St. Louis, MO), “but they seem to have lost their ability to regenerate. If you damage a mammalian utricle, the cells try to divide—they go to DNA replication and just block. We know they try, but they just don't make it.” And in the cochlea, “the cells just do nothing—they don't divide.”

Hair cells in birds readily regenerate, but the behavior of these cells varies according to their location. Only after damage to existing cells do hair cells in the cochlea regenerate, whereas in the utricle these cells turn over frequently, and have a life span of only two to six weeks.

With this in mind, Lovett and his colleagues investigated which genes might be responsible for regulating the growth and regeneration of hair cells. To examine which genes were expressed in each organ, they conducted an innovative cross-species microarray analysis, hybridizing selected gene probes from the human inner ear against cDNA targets derived from epithelia of the chicken utricle or cochlea (Hum. Mol. Genet., 1 June).

These assays, in conjunction with other comparative genetic screens, identified ∼80 genes that seemed to be differentially expressed in either the cochlea or the utricle of the chicken. Among the genes identified as playing an apparent role in hair cell maintenance were GATA-3, a transcription factor previously linked to neuronal and inner ear development and maturation, and cKIT, which encodes a signaling protein linked with deafness in at least one human pedigree.

Lovett and his colleagues anticipate that this study will not only identify potentially valuable genetic markers for deafness but also serve as the foundation for future studies examining gene expression in regenerating patches of avian hair cells, with the aim of identifying the mechanisms behind the restoration of hair cell growth.