NIDCD Scientists Report New Findings on Inner Ear Hair Cell Stereocilia Formation
Scientists at the National Institute on Deafness and Other Communication
Disorders (NIDCD) report that they have discovered some key mechanisms
underlying how stereocilia the tiny hair-like projections jutting
from the top surface of hair cells develop to form their characteristic
architecture. NIDCD scientist Dr. Inna Belyantseva and her co-authors
reported their findings in the February issue of Nature Cell Biology.
The research also was supported by the National Heart, Lung, and
Blood Institute, another component of the National Institutes of
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.