Genes, deafness, and balance disorders

The mammalian auditory sense organ is subdivided into three principle compartments, the outer-, middle- and inner ear. The main task of the outer- and middle ear is to channel sound waves towards the cochlea within the inner ear. The inner ear also contains the vestibule, the end organ for the perception of gravity and acceleration. Hair cells within the sensory epithelia of the cochlea and the vestibule contain stereocilia that harbor mechanically gated ion channels. These ion channels open or close upon deflection of the stereocilia leading to changes in cell polarization and the rate of neurotransmitter release from hair cells onto sensory neurons. In this way, mechanical signals evoked by sound waves or head movement are transformed into electrochemical signals. The positional cloning of human disease genes and the analysis of mouse mutants has led to the identification of numerous genes that cause deafness and balance disorders. These findings provide insights into the molecular and cellular requirements for mechanosensory transduction and establish an entry point to understand deafness at the molecular level. We will summarize results that have shed light on the function of extracellular matrix glycoproteins, cell adhesion molecules, and components of the actin cytoskeleton in the inner ear.