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New clues to human deafness found in mice

PLOS

Researchers at Washington University School of Medicine in St. Louis have identified a gene that is required for proper development of the mouse inner ear, which may help us understand the genetic causes of deafness.

In humans, this gene is known as FGF20, and it has been associated with inherited deafness in otherwise healthy families. The FGF20 gene codes for one member of a family of proteins known as fibroblast growth factors. In general, members of this family are known to play important and broad roles in embryonic development, tissue maintenance and wound healing.

"When we inactivated FGF20 in mice, we saw they were alive and healthy," says senior author David M. Ornitz, MD, PhD, Professor of Developmental Biology. "But then we figured out that they had absolutely no ability to hear."

The results, published online 3 January 2012 in the open-access journal PLoS Biology, show that disabling the gene causes a loss of outer hair cells, a special type of sensory cell in the inner ear responsible for amplifying sound. While about two-thirds of the outer hair cells were missing in mice without FGF20, the number of inner hair cells (responsible for transmitting the amplified signals to the brain), appeared normal.

"This is the first evidence that inner and outer hair cells develop independently of one another," says first author Sung-Ho Huh, PhD, postdoctoral research associate. "This is important because most age-related and noise-induced hearing loss is due to the loss of outer hair cells."

The researchers speculate that FGF20 signaling will be a required step towards regenerating outer hair cells in mammals, and that this pathway may help us understand how mammals differ from birds and other vertebrates in being incapable of performing such hearing restoration naturally.

Beyond being a simple 'on/off' switch, Ornitz and his colleagues found that FGF20 signaling (or its chemical equivalent, FGF9) must occur on or before day 14 of the embryo's development to produce a normal inner ear. Even if FGF20 or FGF9 signaling was activated on day 15 or later, the inner ear still did not develop properly. This critical time point does not exist in other non-mammalian vertebrates that retain the ability to form new hair cells throughout their lives. Whether FGF20 plays a role in this regeneration mechanism remains an important open question. Finally, Ornitz and his colleagues also see evidence that mutations in FGF20 may play a role in human deafness, which is another open question currently being investigated.

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Funding: This work was funded by the Department of Developmental Biology, the Hearing Health Foundation (SH), Action on Hearing Loss, contributions from Edward and Linda Ornitz, NIDCD grant DC006283 (MEW) and NIH support grants (P30DC04665, P30DK052574, and P30AR057235). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Huh S-H, Jones J, Warchol ME, Ornitz DM (2012) Differentiation of the Lateral Compartment of the Cochlea Requires a Temporally Restricted FGF20 Signal. PLoS Biol 10(1): e1001231. doi:10.1371/journal.pbio.1001231

CONTACT:
Prof. David Ornitz
Washington University School of Medicine
Department of Molecular Biology and Pharmacology
Campus Box 8103
660 South Euclid Avenue
St. Louis, MO 63110
UNITED STATES
Tel: +1 (314) 362-3908
dornitz@wustl.edu

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