Notch1 is Required to Maintain Supporting Cell Identity and Vestibular Function during Maturation of the Mammalian...

The inner ear houses both hearing and balance sensory modalities. The hearing and balance organs consist of similar cell types, including sensory hair cells and associated supporting cells. Previously we showed that Notch1 is required for maintaining supporting cell survival during cochlear maturation. To understand the role of Notch during vestibular maturation, we deleted Notch1 from the vestibular organs of both male and female mice at birth. Histological analyses showed a reduction of supporting cells accompanied by an increase in type II hair cells, indicating a conversion of supporting cells to hair cells. Analysis of mature sensory organs indicate the converted hair cells survive, despite a severe reduction of supporting cells. Vestibular sensory evoked potentials (VsEPs), thought to be generated within the striola regions of the maculae, were absent, indicating that NOTCH1 is critical for striolar function. Specialized type I hair cells in the striola failed to develop the complex calyces typical of these cells. Notch1 mutants did not exhibit vestibular behaviors such as circling and head shaking but showed difficulties with tests of balance and swimming. These results indicate that, unlike the cochlea, supporting cells in balance organs retain the plasticity to convert to hair cells which can survive into adulthood. Despite hair cell survival, vestibular function is compromised likely due to the loss of supporting cells and altered innervation.