The vertebrate inner ear arises from an ectodermalthickening, the otic placode, that forms adjacent to thepresumptive hindbrain. Previous studies have suggestedthat competent ectodermal cells respond to Fgf signalsfrom adjacent tissues and express two highly related pairedbox transcription factors Pax2a and Pax8 in the developingplacode. We show that compromising the functions of bothPax2a and Pax8 together blocks zebrafish ear development,leaving only a few residual otic cells. This suggests thatPax2a and Pax8 are the main effectors downstream of Fgfsignals. Our results further provide evidence that pax8expression and pax2a expression are regulated by twoindependent factors, Foxi1 and Dlx3b, respectively.Combined loss of both factors eliminates all indications ofotic specification. We suggest that the Foxi1-Pax8 pathwayprovides an early ‘jumpstart’ of otic specification that ismaintained by the Dlx3b-Pax2a pathway.