Molecular studies of hair cell development and survival.

The development of hair cells in both the auditory and vestibular sensory epithelia is a complex process that involves the coordinated expression of many regulatory proteins. Among these is the POU-domain transcription factor Brn-3.1. This factor is expressed in hair cell precursors immediately after commitment to the hair cell fate, and continues throughout life. Deletion of this factor in mice leads to failure of hair cell differentiation during development, and to the death of a majority of the undifferentiated cells. Normal expression of Brn-3.1 is required for adult hair cell survival as well, since a mutation in this gene causes dominant, late-onset, inherited hearing loss in humans. The timing of the onset of Brn-3.1 expression suggests that factors regulating its expression may be involved in fate determination of hair cells. Moreover, genes that are themselves directly regulated by Brn-3.1 appear to play critical roles in hair cell development and survival.