Nectin KO mice became deaf due to loss of hair cells. Left: the organ of Corti of a normal mouse (control). The hair cells and their supporting cells are aligned in an alternating checkerboard pattern. Right: The organ of Corti of a nectin KO mouse. The upper row of images was taken at 12 days, the lower row at 28 days. 2 weeks after birth, the hair cells of nectin KO mice disappeared due to apoptosis (cell death). The white arrows indicate where the hair cells have attached to each other. Credit: Frontiers of cell biology and development (2022). DOI: 10.3389/fcell.2022.1073830
A Japanese research group has become the first to reveal that the checkerboard pattern of cells in the inner ear organ of Corti is vital for hearing. This finding provides new insight into how hearing works from the perspective of cellular self-organization and will also lead to a better understanding of various hearing loss disorders.
The research group included Assistant Professor Togashi Hideru of Kobe University Graduate School of Medicine and Dr. Katsunuma Sayaka of Hyogo Prefectural Children’s Hospital in Kobe.
These research results have been published online in Frontiers of cell biology and development on December 8, 2022.
The cochlea in the inner ear is needed to hear sound, and inside is the organ of Corti. When the organ of Corti is viewed from above with a microscope, two types of cells can be seen arranged in a precisely ordered arrangement resembling a game of chess or a checkerboard. The hair cells that transmit sound waves to the brain are separated by support cells, which prevent the Hair cells to touch. Although this checkerboard arrangement was thought to be necessary for proper functioning of the organ of Corti, the relationship between this pattern and auditory function has long remained unclear.
This research group previously revealed that this inner ear checkerboard pattern is formed by a cell segregation mechanism that allows hair cells and supporting cells to align properly. Hair cells and supporting cells each express a different type of nectin, the cell adhesion molecule. As a result, a hair cell and a supporting cell adhere more strongly to each other than would two hair cells or two supporting cells.
This property is what causes hair cells and supporting cells to be arranged in a checkerboard pattern. In one mouse model When one of these nectin molecules is not functional, the properties change and the checkerboard pattern cannot form properly. In this study, the researchers used these mice to investigate the link between the checkerboard arrangement of cells and auditory functionality.
The research group compared regular mice (controls) with mice that had one type of nectin that did not work properly (Nectin-3 KO mice, hereafter referred to as Nectin KO mice). No difference between mice was observed in the number of hair cells and supporting cells in the organ of Corti immediately after birth. However, there was a difference in how easily the two cell types adhere to each other; In the nectin-3 KO mouse, hair cells adhere together (which normally does not occur), resulting in abnormalities in the checkerboard pattern.
At this point, the researchers hypothesized that testing the hearing of these mice might reveal the relationship between hearing and the checkerboard pattern. They measured the hearing of nectin KO mice over one month old using the auditory brainstem response (ABR) method. This test revealed that the nectin KO mice were moderately deaf, demonstrating that this hearing loss was caused by the abnormalities of the inner ear.
The researchers then examined the Corti organs of nectin KO mice that underwent the ABR test and found that the number of hair cells had decreased by about half. Next, they investigated why only the hair cells (and not the supporting cells) had disappeared. They found that after two weeks of age, hair cell apoptosis occurs. Additionally, examination of traces of apoptosis revealed that cell death occurred in many cells that had adhered to each other. This led researchers to speculate that hair cells sticking together (which normally doesn’t happen) cause apoptosis.
In the epithelial tissue, which also includes the organ of Corti, there are tight junctions between each cell. These tight seals not only connect cells, but they also prevent various molecules (including ions) from passing between cells. If the organ of Corti does not have these tight joints, the hair cells cannot function properly, the cells die, and hearing loss occurs. In nectin KO mice, tight junctions did not form properly where the hair cells adhered.
However, tight seals formed correctly between the hair cells and supporting cells. As long as two hair cells were not glued together, normal cell function remained. In other words, hair cell apoptosis was only induced where hair cells were abnormally attached to each other and tight joints were not forming properly. These results revealed for the first time that the checkerboard pattern of hair cells and supporting cells found in the organ of Corti functions as a fundamental structure, which protects hair cells and their functionality, by preventing hair cells from s attach to each other.
Nectin is the gene responsible for Margarita Island ectodermal dysplasia. In addition to one cleft lip or palate and intellectual disabilities, deafness has also been reported in some cases of this genetic condition. Therefore, the results of the current study may provide a new explanation for some cases of deafness whose cause is unclear.
This study focused on audience and demonstrated the physiological significance of the checkerboard cell mosaic pattern in the organ of Corti. However, others sensory cells which respond to external stimuli and their respective support cells are also arranged in the same type of alternating mosaic pattern. These mosaic patterns are found in sensory organs, such as the olfactory epithelium which is responsible for smell and the retina which is responsible for vision.
The fact that these mosaic patterns are not only found in mammals but also in a variety of other organisms suggests that they are functionally important. Mosaic patterns in sensory tissues are created by self-organization due to differences in adhesion between cells. Therefore, focusing research on cellular self-organization in sensory organs will increase our knowledge of sensory organ functions and advance our understanding of various related diseases.
More information:
Sayaka Katsunuma et al, Hearing loss in mice with disruption of auditory epithelial patterning in the cochlea, Frontiers of cell biology and development (2022). DOI: 10.3389/fcell.2022.1073830
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Kobe University
Quote: A checkerboard pattern of inner ear cells lets us hear (2022, December 27) Retrieved December 28, 2022, from https://phys.org/news/2022-12-checkerboard-pattern-ear-cells -enables.html
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