For the first time, a Japanese research team has demonstrated the significance of the organ of Corti’s checkerboard-like cell configuration for hearing. The finding offers fresh insight into the functionality of hearing from the point of cellular self-organization and will help researchers better understand the many hearing loss illnesses.
The research team includes Dr. Katsunuma Sayaka of Hyogo Prefectural Kobe Children’s Hospital and Assistant Professor Togashi Hideru of Kobe University’s Graduate School of Medicine.
On December 8, 2022, Frontiers in Cell and Developmental Biology published these study findings online.
The organ of Corti, which is situated inside the cochlea of the inner ear, is required for hearing sound. Two distinct cell types may be identified when the organ of Corti is seen under a microscope. These cells are organized in an intricate pattern that resembles a chess or checkerboard. Support cells separate the hair cells, preventing them from coming into contact with one another as they transmit sound waves to the brain. The link between this checkerboard pattern and hearing capability has long been unknown, despite the fact that it has been assumed that this layout is required for the organ of Corti to function properly.
This study team previously discovered that the cellular segregation process that creates the inner ear checkerboard allows the hair cells and support cells to move into line appropriately. The cell adhesion molecule nectin is expressed differently by support and hair cells. This leads to stronger adhesion between a hair cell and a support cell than between two hair cells or two support cells.
This feature is what results in the checkerboard-like arrangement of hair cells and support cells. When one of these nectin molecules in a mouse model isn’t working, the features alter and the checkerboard pattern doesn’t develop properly. These mice were utilized in this investigation to examine the relationship between the checkerboard configuration of cells and functional hearing.
The study team compared normal (control) mice with animals that lacked a particular form of nectin (nectin-3 KO mouse, referred to as nectin KO mouse below). The number of hair cells and support cells in the organ of Corti shortly after birth did not differ between the mice. However, t here was a variation in which the two types of cells adhered to one another; in the nectin-3 KO animals, hair cells adhered to one another (which is not typical), causing irregularities in the checkerboard pattern.
At this point, the scientists believed that evaluating the mice’s hearing may show how hearing and the checkerboard pattern are related. Using the auditory brainstem response (ABR) technique, they assessed the hearing of nectin KO mice that were more than a month old. This test showed that the nectin KO mice were somewhat deaf, proving that the defects in the inner ear were the source of this hearing loss.
The amount of hair cells had fallen by around half, the researchers discovered after looking at the Corti organs of the nectin KO mice that completed the ABR test. They subsequently set out to determine why just the hair cells had vanished (and not the support cells). They found that hair cell apoptosis took place after two weeks of age. Additionally, analysis of the apoptosis traces showed that several cells that had attached to one another experienced cell death. This prompted the researchers to speculate that the apoptosis was brought on by the hair cells attaching to one another, which is not typical.
The epithelial tissue, which also contains the organ of Corti, has a tight connection. These tight junctions do more than just link the cells together; they also stop numerous chemicals, including ions, from moving back and forth between the cells. Without these tight junctions, the hair cells in the organ of Corti cannot function correctly, the cells die, and hearing loss develop. In the regions where hair cells attached to one another, tight junctions were incorrectly created in nectin knockout mice.
However, between hair cells and support cells, tight junctions did properly form. Normal cell function persisted as long as two hair cells were not attached to one another. In other words, only in regions where tight junctions did not form properly and hair cells were improperly attached to one another was hair cell death triggered. These findings demonstrated for the first time how the organ of Corti’s checkerboard pattern of hair cells and support cells serves as a key component that safeguards hair cells and their activity by preventing hair cells from adhering to one another.
The Margarita Island ectodermal dysplasia gene is nectin. In certain cases of this hereditary condition, deafness has also been recorded in addition to cognitive difficulties and cleft lip or palate. As a consequence, certain cases of deafness where the reason is unknown may now have a new explanation according to the findings of the current study.
This study focused on hearing and illustrated the physiological importance of the mosaic pattern of cells that resembles a checkerboard in the Corti organ. However, similar alternating mosaic patterns are also used to organize additional sensory cells that react to external stimuli and the supporting cells that go with them. These mosaic patterns may be seen in sensory organs like the retina, which is in charge of vision, and the olfactory epithelium, which is in charge of smell.
The fact that these mosaic patterns are present in a wide range of other organisms in addition to mammals shows that they are functionally significant. Due to the variations in cell adhesiveness, sensory tissues develop mosaic patterns through self-organization. As a result, research on cellular self-organization in sensory organs will expand our understanding of different linked disorders as well as our understanding of the functions of sensory organs.
Katsunuma, S., Togashi, H., Kuno, S., Fujita, T., & Nibu, K. I. (2022). Hearing loss in mice with disruption of auditory epithelial patterning in the cochlea. Frontiers in cell and developmental biology, 10, 1073830. https://doi.org/10.3389/fcell.2022.1073830