Gene Governing Development of Hearing Identified

A gene identified by Howard Hughes Medical Institute (HHMI) researchers at Baylor College of Medicine governs a crucial stage in the development of the inner ear.

This discovery, published in the June 11 issue of the journal Science, opens up the possibility of future treatments for millions of Americans who suffer deafness or problems with balance.

Dr. Huda Y. Zoghbi identified a gene called "Mathl" which gives the signal that causes cells in the early stage of development in the inner ear to differentiate and proliferate into hair cells. These hair cells transform sound waves and head motion into information the brain uses for hearing and equilibrium.

For example, if you move your head to the right, fluid in the semicircular canals of the inner ear sets the hair bundles in motion, signaling the brain of the change in position. Sound waves also strike the hair cells and surrounding organs, causing vibrations that are transmitted to the brain and translated as sound.

"Without Mathl, there are no hair cells and no possibility of hearing," says Dr. Zoghbi, Baylor professor and HHMI investigator. She coauthored the Science paper with Dr. Hugo J. Bellen, Baylor professor and HHMI associate investigator.

The collaboration between these two scientists in Baylor's department of molecular and human genetics resulted from their curiosity about uncoordinated fruit flies that lack a gene called atonal. They decided to study how this gene affects development of the nervous system. Drs. Zoghbi and Bellen speculated that atonal would have "relatives," also known as homologs, that govern nervous-system development in vertebrates as well.

Dr. Zoghbi's group isolated the mouse homolog of atonal (Mathl stands for "mouse atonal homolog 1") and the human homolog, HATH1.

To track Math1's activities in mice, the scientists replaced Math1 with a gene whose product turned blue in the presence of a specific chemical. The blue staining would appear in the places where Math1 is normally active.

Dr. Nessan Bermingham, a postdoctoral fellow in Dr. Zoghbi's lab, found that the blue showed up in various areas of the central nervous system and two spots in the inner ear. He then showed that mice without the Mathl gene, called "null mice," never developed the hair-cell bundles crucial to hearing, motion, and balance.

Drs. Zoghbi and Bellen then sought the advice of ear specialists Dr. Anna Lysakowski at the University of Illinois at Chicago and Dr. Ruth Anne Eatock at Baylor College of Medicine.

The mice clearly had early-stage cells that could become either hair cells or supporting cells. The scientists found that although the Math1 null mice developed supporting cells, they did not show any signs of developing hair cells. The researchers deduced that Mathl provided the signal that caused cells to differentiate into hair cells.

The delicate hair cells are vulnerable to disease, aging, and environmental trauma ranging from antibiotics to persistent loud noise. Eventually, this research could lead to treatments for adults whose hearing has been damaged by exposure to extreme noise or by trauma, Dr. Zoghbi says.

More than 28 million Americans suffer impaired hearing.

Vestibular disorders affect one-fourth of the general population and half of the elderly. Once the hair cells are destroyed, they cannot regenerate.

But having the gene that drives hair-cell development in the early stages of life opens up the possibility of therapeutically stimulating new hair-cell growth, thus restoring hearing and balance, Dr. Zoghbi says.

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©2006 Texas Medical Center

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