Notch1 is required to maintain supporting cell identity and vestibular function during maturation of the mammalian balance organs

Abstract

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.Significance Statement While the role of Notch has been investigated thoroughly during cochlear development and maturation, less is known about how Notch regulates vestibular maturation. Here, we show that deletion of Notch1 results in vestibular physiological and behavioral dysfunction by 3 months of age. In contrast to the cochlea, vestibular supporting cells retained the ability to convert to hair cells, and survived into adulthood. However, some specialized hair cells in the central region of the vestibular organs were reduced and not innervated properly. These results show that vestibular supporting cells retain the ability to convert to hair cells during maturation and can be manipulated by altering Notch signaling.