Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells

Mutations in the POU domain gene Brn-3c causes hearing impairment in both t he human and mouse as a result of inner ear hair cell loss. We show here th at during murine embryogenesis, Brn-3c is expressed in postmitotic cells co mmitted to hair cell phenotype but not in mitotic progenitors in the inner ear sensory epithelium. In developing auditory and vestibular sensory epith elia of Brn-3c(-/-) mice, hair cells are found to be generated and undergo initial differentiation as indicated by their morphology, laminar position and expression of hair cell markers, including myosins VI and VIIa, calreti nin and parvalbumin, However, a small number of hair cells are anomalously retained in the supporting cell layer in the vestibular sensory epithelia, Furthermore, the initially differentiated hair cells fail to form stereocil iary bundles and degenerate by apoptosis in the Brn-3c(-/-) mice. These dat a indicate a crucial role for Brn-3c in maturation, survival and migration of hair cells, but not in proliferation or commitment of hair cell progenit ors.