EYA1–SIX1 complex in neurosensory cell fate induction in the mammalian inner ear

The phosphatase-transactivator EYA1 interacts with the homeodomain protein SIX1 to form transcriptional activation complexes, which play essential roles in regulating cell proliferation, survival and induction of sensory and neuronal differentiation programs during inner ear development. Mutations of the Eya1 and Six1 genes cause profound developmental auditory defects in mice and humans. The molecular mechanisms and developmental processes controlled by the EYA1 and SIX1 complex in inner ear development and neurosensory fate induction are the focus of this review.

► The EYA1–SIX1 regulatory network in early inner ear development is discussed. ► Molecular mechanisms by which EYA1–SIX1 drive neuronal induction is discussed. ► Molecular relationships among EYA1–SIX1, SOX2 and ATOH1 for hair cell induction is discussed.