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Hearing and Balance Development Give Mixed Signals

Hearing and Balance Development Give Mixed Signals

Background: During development of the mammalian inner ear, specification of cells to form distinct sensory structures for hearing is known to depend on two important signaling molecules called Shh and Wnt. Earlier research showed that Shh was critical for the development of the auditory cavity or sac into the cochlea for hearing, but little was known about what signaled the development of the vestibular organs necessary for balance. Is Wnt responsible?

Advance: NIDCD-supported scientists created mouse embryos containing a transgene that was modified so that cells activated by the Wnt molecule were distinguishable under the microscope. Wnt signaling was active in the top portion of the inner ear vesicle, turning on genes known to be important for balance formation. An interesting role was discovered for Shh, which initiates gene expression in the bottom vesicle; it was found to also restrict the signaling of Wnt within the top portion of the vesicle. Opposing signals between the Shh and Wnt molecules result in different gene expression between the top (balance) and bottom (hearing) components of the inner ear.

Implications: Balance disorders involving the inner ear include vertigo, loss of balance, and loss of appropriate eye movement control. The proper function of the normal adult vestibular system depends on correct developmental processes to produce the needed structural details of the inner ear. This research shows a balance between Shh and Wnt signaling activities in the embryo and provides critical insight for understanding how molecular mechanisms initiate development of the hearing or balance systems.

Citation: Riccomagno MM, Takada S, Epstein DJ. Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes & Devel 19: 1612-1623, 2005.

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