Inner ear gene discovery offers clues about restoring hearing, balance

A discovery surrounding two genes important for inner ear development could bring closer the day when we can reverse the loss of hearing and balance that results from destruction of hair cells.
Normal and defective inner ear
Absence of Sox11 and Sox4 led to severe malformation of the inner ear structures that contain hair cells (shown here on the right, with normal development on the left).
Image credit: The Rockefeller University

Our inner ear contains hair cells that are important for hearing and balance. Unfortunately, as in all mammals, one of their features is that the final number of hair cells is reached before we are even born. From then on, loud noise, trauma, infections and aging take their toll, until loss of hair cells impairs hearing and balance.

But a new mouse study from The Rockefeller University in New York, NY, published in the Proceedings of the National Academy of Sciences, could help researchers look at new ways to regrow hair cells and restore lost hearing and balance.

The study took place in the sensory neuroscience lab at Rockefeller, which is headed by senior author and professor A. James Hudspeth, a Howard Hughes Medical Institute investigator. The lab work was performed by first author Dr. Ksenia Gnedeva, a postdoctoral researcher.

By examining mice before and after birth, Dr. Gnedeva discovered two genes that could switch on the process of generating hair cells.

Switching genes on led to new hair cells in mature utricles

Dr. Gnedeva began by looking for changes in gene expression in an inner ear structure called the utricle – a small sac or bag-like organ that is lined with hair cells and detects motion.

She eventually spotted that two genes that are highly active before birth become silent after birth, and this dramatic reduction in activity coincides with a halt in the development of hair cells in the mice’s utricles.

The two genes code for the transcription factors Sox4 and Sox11 – proteins that help shape the destiny of precursor cells into their final cell types by regulating the activity of other genes.

On further investigation, Dr. Gnedeva found when both genes were switched off in the developing mice, the entire inner ear, not just the utricle, developed abnormally.

And when she turned the genes on in older mice with fully mature hair cells, she found it led to the regeneration of new hair cells inside fully developed utricles.

Dr. Gnedeva is now exploring the molecular mechanisms that trigger the proteins and what happens afterward. She explains what they hope to find:

“Our ultimate goal is to find a target that would allow us to restore hair cells later on in life. It appears possible that these proteins, or perhaps other steps in the same pathway, might be potential targets.”

More than 90% of hearing loss occurs when either hair cells or auditory nerve cells are destroyed. According to the Centers for Disease Control and Prevention (CDC), around 36 million American adults report some degree of hearing loss.

Scientists at the National Institutes of Health are also poised to make major discoveries on hair cells and hearing loss. A key area of their research that Medical News Today learned about recently is the generation of a genetic blueprint of inner ear cell development.

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