DF/HCC Program Affiliation

Neuro-Oncology

Research Abstract

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.

Publications

• Abraira VE, Hyun N, Tucker AF, Coling DE, Brown MC, Lu C, Hoffman GR, Goodrich LV.Changes in Sef levels influence auditory brainstem development and function.J Neurosci 2007 Apr 18;27(16):4273-82.
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• Deans MR, Antic D, Suyama K, Scott MP, Axelrod JD, Goodrich LV.Asymmetric distribution of prickle-like 2 reveals an early underlying polarization of vestibular sensory epithelia in the inner ear.J Neurosci 2007 Mar 21;27(12):3139-47.
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• Leighton PA, Mitchell KJ, Goodrich LV, Lu X, Pinson K, Scherz P, Skarnes WC, Tessier-Lavigne M.Defining brain wiring patterns and mechanisms through gene trapping in mice.Nature 2001 Mar 8;410(6825):174-9.
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