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, whose loss 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. Here we show that two members of the SoxC family of transcription factors, Sox4 and Sox11, are down-regulated 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.
Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065; Laboratory of Sensory Neuroscience, The Rockefeller University, New York, NY 10065.
Ksenia
K
Gnedeva
Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065; Laboratory of Sensory Neuroscience, The Rockefeller University, New York, NY 10065 hudspaj@rockefeller.edu.
A J
AJ
Hudspeth
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D007758:Ear, Inner / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D055751:SOXC Transcription Factors / Q000502:physiology*; D012444:Saccule and Utricle / Q000033:anatomy & histology; D017423:Sequence Analysis, RNA
D017931:DNA Primers; D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; C489990:Sox4 protein, mouse
auditory system; cochlea; hair cell; utricle; vestibular system