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June 2, 2014
Hearing Different Frequencies
Researchers gained insights into how cells in the auditory system become organized to hear different frequencies. The findings could lead to new approaches for certain kinds of hearing loss.
The human ear can detect a wide range of frequencies, from the low rumbles of distant thunder to the high-pitched whine of a mosquito. The sensory cells that detect these sounds are called hair cells, named for the hair-like strands that cluster on their tops. Hair cells are spread across a flat surface called the basilar membrane, which is rolled like a carpet and tucked into a snail shell-shaped structure in the inner ear called the cochlea.
Each of our roughly 16,000 hair cells is dedicated to a narrow frequency range. These cells are ordered along the basilar membrane according to the frequencies they detect. Those that sense low pitches are at one end; those that detect high pitches are at the other. While this stepwise arrangement of hair cells on the basilar membrane—the tonotopic map—has been known for years, how the cells become ordered this way was unknown.
A research team led by Drs. Zoe F. Mann and Matthew W. Kelley at NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD) suspected that a molecular concentration gradient may guide the cells during development. Like numbers on a ruler, the cell positions might be marked by levels of a signaling molecule.
To investigate, the team examined the auditory organs of 6-day-old chick embryos. The basilar papilla in chickens, like the cochlea in mammals, has hair cells arranged along the length of a basilar membrane according to frequency. The study was published on May 20, 2014, in Nature Communications.
The scientists identified a concentration gradient of bone morphogenetic protein 7 (Bmp7) across the length of the basilar papilla at the time of chick hair cell formation. Bmp7 is a signaling protein produced during embryonic development that is known to play a role in the development of bone and kidneys.
The researchers showed that Bmp7 promotes the development of low-frequency-sensing hair cells. When they bathed developing basilar papillas in a solution containing Bmp7, they found that all the hair cells—even those at the high-frequency end—developed characteristics of low-frequency-sensing hair cells. These results suggest that during embryonic development, high levels of Bmp7 at one end of the basilar papilla signal the formation of low-frequency-sensing hair cells. Decreasing levels of Bmp7 along the length of the basilar papilla map result in a gradual tuning to higher frequencies.
In an accompanying paper in the same journal, a team led by Drs. Benjamin R. Thiede and Jeffrey T. Corwin at the University of Virginia School of
Medicine, working in collaboration with the NIDCD team, revealed that another signaling molecule, retinoic acid, acts in concert with Bmp7 to position cells.
“The findings could open doors to therapies that take advantage of Bmp7’s navigational talents to direct the formation of regenerated sensory cells that are tuned to respond to a specific frequency,” says Dr. James F. Battey, Jr., director of NIDCD. “Since many forms of hearing loss are limited to specific frequencies, this approach could lead to replacement sensory cells that are tailored to individual needs.”
Bmp7 is also found in the inner ear of mammals. Kelley’s team now plans to use mouse models to examine the role of Bmp7 in patterning the mammalian auditory system.
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Reference: A gradient of Bmp7 specifies the tonotopic axis in the developing inner ear. Mann ZF, Thiede BR, Chang W, Shin JB, May-Simera HL, Lovett M, Corwin JT, Kelley MW. Nat Commun. 2014 May 20;5:3839. doi: 10.1038/ncomms4839. PMID: 24845721. Retinoic acid signalling regulates the development of tonotopically patterned hair cells in the chicken cochlea. Thiede BR, Mann ZF, Chang W, Ku YC, Son YK, Lovett M, Kelley MW, Corwin JT. Nat Commun. 2014 May 20;5:3840. doi: 10.1038/ncomms4840. PMID: 24845860.
Funding: NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD) and the American Hearing Research Foundation.