Researchers identify important molecular switch for hearing development
In the inner ear, there are two different types of sensory cells that are responsible for hearing. An MHH research team has now identified the molecular switch for the formation of these inner and outer hair cells and thus found an important building block for the treatment of hearing loss.
The inner and outer hair cells develop before birth from a common type of precursor cells. Which factors control the different development was unknown for a long time. A research team led by Professor Dr. Andreas Kispert and Dr. Mark-Oliver Trowe from the Institute of Molecular Biology at the Hannover Medical School (MHH) has now found the key and demonstrated how it controls the process: The gene Tbx2 acts like a switch to determine whether inner or outer hair cells are formed. The work has been published in the journal Nature Communications.
Vibration transducers and sound amplifiers
More than 400 million people worldwide are affected by hearing loss. The most common is sensorineural hearing loss, in which the hair cells responsible for hearing are destroyed. From birth, we have about 15,000 hair cells in each ear. They are located in the inner ear in the cochlea, and 3,500 of them belong to the inner hair cells. They are the actual sensory cells and convert the vibrations triggered by external sound into electrical signals in the inner ear. These reach the brain via nerve pathways, where the auditory impression is created.
The outer hair cells act as a mechanical amplifier and improve the sensitivity of hearing. Once destroyed, the hair cells can no longer regenerate and the hearing ability decreases. "This happens, for example, due to aging processes, excessive noise or even the intake of certain medications," says Dr. Trowe, head of the study.
Scientists around the world are working to develop therapies that can help renew the auditory sensory cells. "But for this, it is imperative to understand which genes control the formation of hair cells during embryonic development," emphasizes the molecular biologist.
Tbx2 regulates development into inner and outer hair cells
In their investigations, the research team focused on the gene Tbx2. It contains the information for a so-called transcription factor. Like an on-off switch, this protein regulates whether certain genetic information on the DNA should be read or not. "We studied the cochlea in the mouse model and found that Tbx2 is active exclusively in the inner hair cells," says Professor Kispert. If Tbx2 was specifically switched off in the precursor cells, no more inner hair cells formed. If, on the other hand, it was switched on in all precursor cells, only inner hair cells were formed. The importance of the molecular switch for the allocation of hair cells was also shown at a later stage of development.
"If Tbx2 is deactivated in the inner hair cells, they transform into outer hair cells," the scientist explains. "Conversely, activation of Tbx2 in the outer hair cells causes them to convert to inner hair cells."
Since the inner ear of mice and humans is similar, the researchers assume that the regulatory pathways are also transferable. The identification of Tbx2 as a molecular switch for the formation of inner hair cells is therefore an important building block for the development of regenerative therapies for the treatment of hearing loss.
More information: Marina Kaiser et al, TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti, Nature Communications (2022). DOI: 10.1038/s41467-022-35214-4
Journal information: Nature Communications
Provided by Medizinische Hochschule Hannover