SoxC transcription factors are essential for the development of the inner ear
Hair cells, the mechanosensory receptors of the inner ear, underlie the senses of hearing and balance. Adult mammals cannot adequately replenish lost hair cells, which often results in deafness or balance disorders. To determine the molecular basis of this deficiency we investigated the development of a murine vestibular organ, the utricle. We found that two members of the SoxC family of transcription factors, Sox4 and Sox11, are downregulated after the epoch of hair cell development. Conditional ablation of SoxC genes in vivo results in stunted sensory organs of the inner ear and loss of hair cells. Enhanced expression of SoxC genes in vitro conversely restores supporting cell proliferation and the production of new hair cells in adult sensory epithelia. These results imply that SoxC genes govern hair cell production and thus advance these genes as targets for the restoration of hearing and balance.
In representative images of cultured utricles transfected 7 d previously with control (left) or Ad-Sox4-RFP virus, transfected cells are marked by red-fluorescent protein (red) and proliferating cells are labeled for EdU (white). The number of EdU-positive cells rises significantly in Sox4-transfected utricles, indicating that the transcription factor restores the proliferative capacity of supporting cells. Because some of the newly created cell subsequently differentiate into hair cells, this approach may prove useful in the restoration of vestibular and auditory sensitivity.