FGF/FGFR-2(IIIb) signaling is essential for inner ear morphogenesis

Interactions between FGF10 and the IIIb isoform of FGFR-2 appear to be cruc ial for the induction and growth of several organs, particularly those that involve budding morphogenesis. We determined their expression patterns in the inner ear and analyzed the inner ear phenotype of mice specifically del eted for the IIIb isoform of FGFR-2. FGF10 and FGFR-2(IIIb) mRNAs showed di stinct, largely nonoverlapping expression patterns in the undifferentiated otic epithelium. Subsequently, FGF10 mRNA became confined to the presumptiv e cochlear and vestibular sensory epithelia and to the neuronal precursors and neurons. FGFR-2(IIIb) mRNA was expressed in the nonsensory epithelium o f the otocyst that gives rise to structures such as the endolymphatic and s emicircular ducts. These data suggest that in contrast to mesenchymal-epith elial-based FGF10 signaling demonstrated for other organs, the inner ear se ems to depend on paracrine signals that operate within the epithelium. Expr ession of FGF10 mRNA partly overlapped with FGF3 mRNA in the sensory region s, suggesting that they may form parallel signaling pathways within the oti c epithelium. In addition, hindbrain-derived FGF3 might regulate otocyst mo rphogenesis through FGFR-2(IIIb). Targeted deletion of FGFR-2(IIIb) resulte d in severe dysgenesis of the cochleovestibular membraneous labyrinth, caus ed by a failure in morphogenesis at the otocyst stage. In addition to the n onsensory epithelium, sensory patches and the cochleovestibular ganglion re mained at a rudimentary stage. Our findings provide genetic evidence that s ignaling by FGFR-2(IIIb) is critical for the morphological development of t he inner ear.