Brn-3c is a transcription factor necessary for maturation and survival of hair cells in the inner ear. Mutations in Brn-3c are associated with deafness in mice and with hearing loss in humans. Mice lacking Brn-3c also show reduced innervation and loss of sensory neurons presumed to be an indirect effect of hair cell loss potentially through lower BDNF and NT-3 expression. Using transient transfection assays we show that Brn-3c is capable of activating both BDNF and NT-3 promoters in inner ear sensory epithelial cell lines. In vitro analysis shows that Brn-3c binds to specific elements within the promoters of both genes and these elements are sufficient to confer Brn-3c regulation on a heterologous promoter. Additionally, BDNF expression is reduced in the inner ear of a Brn-3c mutant mouse during embryogenesis. Our data suggest that Brn-3c may play a role in regulating neurotrophin gene expression in the inner ear. (C) 2004 Elsevier Inc. All rights reserved.