The mammalian inner ear is a complex sensory organ comprised of auditory and vestibular structures that serve to coordinate the senses of hearing and balance, respectively. The inner ear develops over a protracted period originating from a thickening of surface ectoderm, the otic placode, which forms at the level of the prospective hindbrain upon inductive influences from neighboring tissues (Groves and Bronner-Fraser 2000;Ladher et al. 2000). Once induced, the otic placode invaginates to form the otic cup and shortly thereafter pinches off from the surface ectoderm to give rise to the otic vesicle. Over the next several days the otic vesicle undergoes an intense period of proliferation, differentiation, and morphogenesis culminating in the establishment of the ventrally derived auditory component of the inner ear, the cochlea, as well as the more dorsally derived vestibular apparatus, comprising the semicircular canals, utricle, and saccule (for review, see Torres and Giraldez 1998).Grafting and lineage tracing experiments performed in the chick, in addition to mutational analyses performed in the mouse, have confirmed that the fate of inner ear progenitors is specified early in development (Baker and Bronner-Fraser 2001). By the otic vesicle stage, numerous genes showing restricted patterns of expression compartmentalize the otic epithelium along its three major axes (Fekete and Wu 2002). With respect to the auditory component of the inner ear, the expression of several genes in the ventral and ventromedial regions of the otocyst, including the overlapping expression of the homeobox transcription factors Otx1 and Otx2 as well as the paired-box gene Pax2 mark the location of cochlear duct outgrowth (Fekete and Wu 2002). For vestibular development, the homeobox transcription factors Hmx2, Hmx3, and Dlx5 in the dorsolateral region of the otocyst mark the territory contributing to semicircular canal formation (Fekete and Wu 2002). Loss-of-function studies in the mouse confirm that each of these genes participates actively in establishing regional identity within the inner ear (Acampora et al. 1996(Acampora et al. , 1999Torres et al. 1996;Hadrys et al. 1998;Wang et al. 1998Wang et al. , 2001Depew et al. 1999;Morsli et al. 1999).In addition to the establishment of regional identity, a number of genes have also been identified that have an impact on the specification of distinct cell fates within the otocyst. The inner ear is a self-contained organ in that the majority of cell types contributing to its development including sensory, nonsensory, and neurogenic are derived from the otic epithelium (Torres and Giraldez 1998). For instance, within the anteroventral region of the otic vesicle, cells expressing the bHLH transcription factors Neurogenin-1 (Ngn1) and NeuroD form the neuronal lineage, giving rise to the cochleovestibular