The vertebrate inner ear develops from the otic placode,an ectodermal thickening that forms adjacent to thepresumptive hindbrain. Previous studies have suggestedthat competent ectodermal cells respond to signals fromadjacent tissues to form the placode. Members of the Fgffamily of growth factors and the Dlx family of transcriptionfactors have been implicated in this signal-responsepathway. We show that compromising Fgf3 and Fgf8signaling blocks ear development; only a few scattered oticcells form. Removal of dlx3b, dlx4b and sox9a genestogether also blocks ear development, although a fewresidual cells form an otic epithelium. These cells fail toform if sox9b function is also blocked. Combined loss of Fgfsignaling and the three transcription factor genes, dlx3b,dlx4b and sox9a, also completely eliminates all indicationsof otic cells. Expression of sox9a but not dlx3b, dlx4b orsox9b requires Fgf3 and Fgf8. Our results provide evidencefor Fgf3- and Fgf8-dependent and -independent geneticpathways for otic specification and support the notion thatFgf3 and Fgf8 function to induce both the otic placode andthe epithelial organization of the otic vesicle.