Hearing loss in mice with disruption of auditory epithelial patterning in the cochlea.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.
Multivalent afadin interaction promotes IDR-mediated condensate formation and junctional separation of epithelial cells.In epithelial cells, cell-cell adhesion is mediated by the apical junctional complex (AJC), which consists of tight junctions (TJs) and adherens junctions (AJs) aligned from the apical to the basal axis. However, the mechanism of AJC formation on the apical side and the separation of these junctions within AJCs are poorly understood. We find that multivalent interactions of afadin with adhesion molecules and the cytoskeleton lead to condensate formation in an intrinsically disordered region (IDR)-dependent manner, which promotes efficient accumulation in the linear AJ during initial junction formation. Furthermore, we observe that afadin and ZO-1 induce different condensate formations in the cell and that these molecules are differentially distributed from each other. These properties of afadin explain how it strictly localizes to AJs in epithelial cells and is involved in regulating the segregation of AJs and TJs within the AJC.
