In the organ of Corti in the inner ear, there are 2 types of cells set up in a checkerboard-like mosaic pattern; hair cells accountable for hearing and their assistance cells. However, the relationship between this checkerboard pattern and hearing function has long remained unclear.
In mice in which the cells in the organ of Corti might not form into this checkerboard pattern, just the hair cells passed away (apoptosis), which led to deafness.
For the very first time worldwide, it was comprehended that the checkerboard design plays a basic structural role in protecting hair cells and their performance as the arrangement prevents hair cells from sticking to each other.
This mosaic pattern of cells has actually been observed in numerous sensory organs in several kinds of animals. Comprehending the mechanism behind how cell self-organization forms these mosaic patterns will help illuminate the functions of a range of sensory organs and the mechanisms behind conditions.
Hair cells that communicate sound waves to the brain are separated by support cells, which prevent the hair cells from touching each other. Hair cells and assistance cells each reveal a various type of the cell adhesion molecule nectin. There was a difference in how easily the two types of cell adhere to each other; in the nectin-3 KO mice hair cells adhere together (which does not normally occur) resulting in abnormalities in the checkerboard pattern. In other words, hair cell apoptosis was caused only in the places where hair cells were abnormally adhered to each tight and other junctions did not form correctly. These results exposed for the very first time that the checkerboard pattern of hair cells and assistance cells discovered in the organ of Corti works as a fundamental structure, which safeguards hair cells and their performance, by avoiding hair cells from becoming connected to each other.
Organ of Corti: The sensory organ responsible for hearing. It is situated inside the cochlea in the inner ear.
Auditory brainstem reaction (ABR): A method of taping the brain waves that are created when noise is heard. ABR is not just utilized to evaluate the hearing of newborn human infants, it can also be used on mice and other animals.
Apoptosis: A kind of set cell death or cellular suicide that happens in multicellular organisms.
Margarita Island ectodermal dysplasia: A congenital disease triggered by mutations in the nectin-1 gene. The primary manifestation is a cleft lip or palate accompanied by intellectual disability.
Reference
” Hearing loss in mice with disturbance of auditory epithelial pattern in the cochlea” by Sayaka Katsunuma, Hideru Togashi, Shuhei Kuno, Takeshi Fujita and Ken-Ichi Nibu, 8 December 2022, Frontiers in Cell and Developmental Biology.DOI: 10.3389/ fcell.2022.1073830.
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This research study got financing from the following organizations: KAKENHI grants from the Japan Society for the Promotion of Science (JSPS) (grant numbers: 18H04764, 18K09319, 19H04965, 22K19331), the Japan Science and Technology Agencys Presto program (JPMJPR1946) and the Takeda Science Foundation.
Main Points
Research study Background
The inner ear cochlea is necessary for hearing noise, and located inside it is the organ of Corti (* 1). When the organ of Corti is viewed from above under a microscope, 2 types of cells set up in a specifically ordered layout looking like a chess or checkerboard can be seen. Hair cells that convey acoustic waves to the brain are separated by support cells, which avoid the hair cells from touching each other. It has actually been thought that this checkerboard arrangement is required for the organ of Corti to operate properly, the relationship between this pattern and hearing function has long stayed unclear.
This research group formerly exposed that this inner ear checkerboard is formed by a cellular segregation system that allows the hair cells and support cells to move into line properly. Hair cells and support cells each express a different type of the cell adhesion molecule nectin. This results in a hair cell and a support cell sticking more highly to each besides two hair cells or 2 support cells would. This property is what causes hair cells and support cells to be set up in a checkerboard pattern. In a mouse design where among these nectin molecules is not practical, the homes change and the checkerboard pattern can not form correctly. In this study, the researchers utilized these mice to examine the connection between the checkerboard arrangement of cells and hearing functionality.
Research study Methodology
The research study group compared regular (control) mice to mice with one type of nectin not working properly (nectin-3 KO mouse, referred to as nectin KO mouse listed below). No distinction in between the mice was observed in the number of hair cells and support cells in the organ of Corti right away after birth. There was a difference in how quickly the 2 types of cell adhere to each other; in the nectin-3 KO mice hair cells adhere together (which does not usually occur) resulting in abnormalities in the checkerboard pattern.
Next they set out to find out why only the hair cells (and not the support cells) had vanished. In addition, examination of the traces of apoptosis revealed that cell death occurred in numerous cells that had adhered to each other.
In the epithelial tissue, which likewise consists of the organ of Corti, there are tight junctions between each cell. These tight junctions not just connect the cells, they also prevent various molecules (consisting of ions) from passing between the cells. If the organ of Corti does not have these tight junctions, hair cells can not operate correctly, cells pass away and hearing loss happens. In nectin KO mice, tight junctions were not formed properly in the locations where hair cells adhered together. Tight junctions did correctly form in between hair cells and support cells. As long as two hair cells were not adhered together, regular cell function remained. Simply put, hair cell apoptosis was caused only in the locations where hair cells were unusually adhered to each tight and other junctions did not form properly. These results exposed for the first time that the checkerboard pattern of hair cells and support cells discovered in the organ of Corti functions as a fundamental structure, which safeguards hair cells and their performance, by avoiding hair cells from ending up being attached to each other.
Further Research
Nectin is the causal gene for Margarita Island ectodermal dysplasia (* 4). In addition to a cleft lip or palate and intellectual specials needs, deafness has likewise been reported sometimes of this hereditary condition. The results of the existing research study may provide a new explanation for some cases of deafness where the cause is uncertain.
This research study concentrated on hearing and showed the physiological significance of the checkerboard-like mosaic pattern of cells in the organ of Corti. Other sensory cells that respond to outdoors stimuli and their respective advocate cells are also arranged in the same kind of alternating mosaic pattern. These mosaic patterns are discovered in sensory organs, such as the olfactory epithelium that is responsible for the sense of odor and the retina which is accountable for vision. The reality that these mosaic patterns are not just discovered in mammals however likewise in a range of other organisms recommends that they are functionally important. The mosaic patterns in sensory tissues are created by self-organization due to the differences in adhesiveness in between cells. For that reason, focusing research on cellular self-organization in sensory organs will increase our knowledge of the functions of sensory organs and advance our understanding of various associated illness.
Glossary
Left: The organ of Corti from a regular (control) mouse. The hair cells and their support cells are lined up in a rotating, checkerboard-like pattern. Right: The organ of Corti from a nectin KO mouse. The leading row of images were taken at 12 days old, the bottom row at 28 days old. 2 weeks after birth, the hair cells in nectin KO mice disappeared due to apoptosis (cell death). The white arrows suggest where hair cells became attached to each other. Credit: Katsunuma S, Togashi H, Kuno S, Fujita T and Nibu K-I (2022) Hearing loss in mice with disruption of auditory epithelial pattern in the cochlea. Front. Cell Dev. Biol. 10:1073830
A Japanese research study group has actually become the first to expose that the checkerboard-like arrangement of cells in the inner ears organ of Corti is important for hearing. The discovery provides a new insight into how hearing works from the point of view of cell self-organization and will also allow numerous hearing loss conditions to be better understood.
The research study group consisted of Assistant Professor Hideru Togashi of Kobe Universitys Graduate School of Medicine and Dr. Sayaka Katsunuma of Hyogo Prefectural Kobe Childrens Hospital.
These research results were published online in Frontiers in Cell and Developmental Biology on December 8, 2022.