The role of Wnt signaling in inner ear development

Components of the Wnt signaling pathway are expressed in the developing inner ear. Wnt3a was shown to be expressed in the dorsal otic epithelium, and then becomes confined to the developing endolymphatic duct. To explore the role of Wnt signaling in ear patterning, we activated Wnt signaling globally in the otic epithelium using retroviral gene vectors to force expression of wnt3a or an activated form of β-catenin, which should constitutively activate Wnt target genes. In experimental ears infected with the activated β-catenin virus, at embryonic day 9 (E9), morphological defects were apparent and included hypomorphic semicircular canals, evaginations of the basilar papilla, enlarged cochlear ducts and malformed vestibules. Several sensory patches within the vestibule were fused although initial hair cell numbers appeared unchanged. At E11-18, experimental cochleae contained small ectopic otoliths and otolithic membranes (the extracellular matrix of vestibular maculae) overlying the basilar papilla (an auditory organ). Beneath the ectopic otoliths were unusual patches of hair cells with vestibular stereociliary bundle morphology. Vestibular hair cell patches appeared at a variety of proximal-distal positions within the basilar papilla and in non-sensory portions along the superior side of the cochlear duct. The same regions stained with a marker of vestibular supporting cells. Expression of msx1 and p75ngfr suggested that the aberrant patches had assumed the identity of a subtype of vestibular maculae, either the lagena macula or the macula neglecta. These results suggest that activating the Wnt/β-catenin signaling pathway either converts parts of the auditory sensory organ to a vestibular macula fate or allows the organs to merge. Forced expression of wnt3a in the cochlear duct phenocopied the ectopic otoliths and vestibular patches seen with the activated β-catenin. We hypothesize that Wnts may establish either the identity or the boundaries of the sensory organs in the inner ear