Hearing loss in mice with disruption of auditory epithelial patterning in the cochlea

Abstract

In the cochlear auditory epithelia, sensory hair and supporting cells are arranged in a checkerboard-like mosaic pattern, which is conserved across a wide range of species. The cell adhesion molecules nectin-1 and nectin-3 are required for this pattern formation. The checkerboard-like pattern is thought to be necessary for auditory function, but has never been examined. Here, we showed the significance of checkerboard-like cellular pattern in the survival and function of sensory hair cells in the cochlear auditory epithelia of nectin-3 knockout (KO) mice. Nectin-3 KO mice showed progressive hearing loss associated with degeneration of aberrantly attached hair cells via apoptosis. Apoptotic hair cell death was due to the disorganization of tight junctions between the hair cells. Our study revealed that the checkerboard-like cellular pattern in the auditory epithelium provides a structural basis for ensuring the survival of cochlear hair cells and hearing function.

A Cellular Potts Model of the interplay of synchronization and aggregation

“…The possibility of persistent checkerboard patterns as one of the phases in our model is particularly interesting, since such checkerboard patterns are found in vivo in the auditory sensory epithelium of the cochlea of many species, composed of sensory hair cells and supporting cells ( Togashi et al, 2011 ; Katsunuma et al, 2022 ). Both hair cells and supporting cells differentiate from pluripotent ectodermal cells ( Wan, Corfas & Stone, 2013 ).…”

“…Instead, we seek to provide an investigation of the broad types of patterns in space and synchronizations that are possible with a set of minimal assumptions. However, we discuss potential applications to concrete findings about pattern formation in the auditory sensory epithelia of many species, where checkerboard patterns composed of sensory hair and supporting cells are established in development and crucial for proper functioning ( Togashi et al, 2011 ; Katsunuma et al, 2022 ).…”