The Transcription Factor Sox2 Is Required to Maintain the Cell Type-Specific Properties and Innervation of Type II...

The sense of balance relies on vestibular hair cells, which detect head motions. Mammals have two types of vestibular hair cell, I and II, with unique morphological, molecular, and physiological properties. Furthermore, each hair cell type signals to a unique form of afferent nerve terminal. Little is known about the mechanisms in mature animals that maintain the specific features of each hair cell type or its postsynaptic innervation. We found that deletion of the transcription factor Sox2 from Type II hair cells in adult mice of both sexes caused many cells in utricles to acquire features unique to Type I hair cells and to lose Type II-specific features. This cellular transdifferentiation, which included changes in nuclear size, chromatin condensation, soma and stereocilium morphology, and marker expression, resulted in a significantly higher proportion of Type I-like hair cells in all epithelial zones. Furthermore, Sox2 deletion from Type II hair cells triggered non-cell autonomous changes in vestibular afferent neurons; they retracted bouton terminals (normally present on only Type II cells) from transdifferentiating hair cells and replaced them with a calyx terminal (normally present on only Type I cells). These changes were accompanied by significant expansion of the utricle's central zone, called the striola. Our study presents the first example of a transcription factor required to maintain the type-specific hair cell phenotype in adult inner ears. Furthermore, we demonstrate that a single genetic change in Type II hair cells is sufficient to alter the morphology of their postsynaptic partners, the vestibular afferent neurons.SIGNIFICANCE STATEMENT The sense of balance relies on two types of sensory cells in the inner ear, Type I and Type II hair cells. These two cell types have unique properties. Furthermore, their postsynaptic partners, the vestibular afferent neurons, have differently shaped terminals on Type I versus Type II hair cells. We show that the transcription factor Sox2 is required to maintain the cell-specific features of Type II hair cells and their postsynaptic terminals in adult mice. This is the first evidence of a molecule that maintains the phenotypes of hair cells and, non-cell autonomously, their postsynaptic partners in mature animals.