The Goodrich laboratory uses mouse genetics to study the patterning and wiring of the inner ear, which houses the sensory organs for hearing and balance. We have identified a handful of proteins that are required for normal auditory and vestibular function, including Lrigs, Fat cadherins, GATA3, and Mafb. Mutations in these genes result in significant changes in cell behavior in the developing inner ear, from changes in cell archictecture (Fat) to changes in cell survival (GATA3). We are particularly interested in the Lrigs, as they represent a novel family of Ig superfamily proteins with unknown functions. We have found that Lrig3 regulates the formation of the three-dimensional structure of the inner ear by determining when and where the basal lamina breaks down in the early otic vesicle. Since Lrig genes are frequently deleted in human cancers, we are investigating the possibility that Lrig signaling represents a novel mechanism of basal lamina breakdown and hence tumor metastasis.