NIDCD Scientists Report New Findings On Inner Ear Hair Cell Stereocilia Formation

Dr. James F. Battey, director of NIDCD, said this work provides “important new information about the molecular basis for normal hair cell development and offers promise for future efforts in understanding some forms of hereditary deafness at the molecular and genetic level.”

Hearing takes place at the level of the inner ear hair cells — the basic sensory elements of hearing. Stereocilia are essential components for the normal hearing process since they convert mechanical energy of sound pressure into electrical signals, which sensory hair cells then direct to the brain. This conversion of sound stimuli into electrical signal, also known as mechanoelectrical transduction, is possible only when stereocilia are organized into bundles with a characteristic staircase-like appearance due to closely positioned rows of stereocilia of increasing heights. Abnormalities of this staircase-like architecture can lead to deafness and balance problems.

Two strains of mice, shaker 2 and whirler, with abnormally short inner ear hair cell stereocilia lacking mature, staircase-like appearance, are deaf. Mutations of two known genes, myosin-XVa and whirlin, underlie stereocilia pathology in shaker 2 and whirler mice. Belyansteva and co-authors found that protein products of these two genes work together to elongate stereocilia rows to the mature length. The authors also have been able to correct the genetic abnormality of stereocilia formation in hair cells from shaker 2 and whirler deaf mice.

Belyantseva and co-authors report that hair cells from shaker 2 mice with short stereocilia were maintained in culture and after injection with a compact form of the gene (cDNA) for myosin-XVa, the normal hair cell stereocilia staircase architecture was restored. But myosin-XVa doesn’t do the job alone. It acts as a type of molecular motor to transport whirlin from the cell body to the top of the stereocilia, where elongation takes place. The researchers believe that this is only one of many mechanisms necessary to construct stereocilia. Mouse hair cells containing the defective gene for whirlin also were maintained in culture and a normal cDNA for whirlin was added back to these cells that have short stereocilia. Once again, introducing a functional cDNA for whirlin resulted in the formation of a normal stereocilia staircase structure.

Finally, the researchers conclude that interaction of myosin-XVa and whirlin is needed for the development of mature stereocilia bundle architecture. Furthermore, replacing defective copies of these two genes with corresponding normal cDNA in hair cells taken from deaf mice even after birth was able to restore the normal appearance of stereocilia. This finding could have future implications for a possible cure of some forms of hereditary deafness in humans and mice. But they caution that much research is needed before this phase of the work can be successfully attempted. In the meantime, they will continue to work to identify the other proteins and genetic components necessary for normal stereocilia development.

NIDCD is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIDCD sponsors research and research training on normal and disordered processes of hearing, balance, smell, taste, voice, speech, and language.