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Regenerating Auditory Hair Cells is Elementary Genetics

Background: As they assume their mature identities during development, mammalian auditory hair cells stop dividing. Cyclin dependent kinases (CDKs) are molecules that tell cells to divide. CDKs are actively regulated by CDK inhibitors (CKIs), which are molecules that tell cells to stop dividing. Together, CDKs and CKIs work together to maintain mature hair cells in a continuous non-dividing state. In practical terms, this means that the auditory hair cells of the inner ear cannot regenerate if they are damaged or lost because of trauma, injury or disease. Moreover, it is likely that CDKs and CKIs play a role in hearing loss, but the actual mechanism is largely unexplored.

Advance: The first scientific relationship between CKIs and the auditory system was determined by NIDCD-supported scientists. They examined the ears of mice that lack two forms of CKIs, Kip1 and Ink4d. Without the CKIs, more than the normal number of sensory hair cells developed in both sets of mice. Despite the presence of extra hair cells, all the mice became hearing impaired soon after birth. Scientists determined that the animals’ hearing loss was due to loss of hair cells.

Implications: These data emphasized the importance of CKI pathways in the active homeostasis of the auditory system. Although there are currently no mutations for hearing loss mapped to the gene for Ink4d in humans (CDKN2D ), these data suggest that a mutation, or disruption of a similar gene could potentially cause human hearing loss.

Chen P, Zindy F, Abdala C, Liu F, Li X, Roussel MF, Segil N. Progressive Hearing Loss in Mice Lacking the Cyclin Dependent Kinase Inhibitor Ink4d. Nat Cell Bio 5:422-426, 2003.