Human Genetics

E-mail: suzi.mansour@genetics.utah.edu
Address: 7110a Eccles Institute of Human Genetics
Phone: 585-6893

FGF Signaling in Development and Function of the Peripheral Auditory System

Research description:  The inner ear, which mediates the sensations of hearing and balance, is derived almost entirely from a small patch of ectodermal cells that are specified for an otic fate early in fetal development. Through a series of tissue interactions mediated by secreted signaling molecules, otic cells undertake complex processes of morphogenesis and differentiation to generate a functional inner ear. Fibroblast growth factor (FGF) signaling plays critical roles at all stages of inner ear development and decreasing or increasing flow through the FGF signaling pathway leads to congenital deafness, which is the most common human sensory disorder. My laboratory employs genetic and molecular approaches to characterize FGF signaling pathway components important for the development and/or function of the mouse inner ear and to model human hearing loss phenotypes.

One possible project for a summer student arises from our studies of a mouse model of Muenke Syndrome, which is caused by an activating mutation in FGF receptor 3 (FGFR3P250R), and exhibits dominant hearing loss due to a cell fate change in the cochlea (preliminary data). To determine which FGF ligand is responsible for activating the mutant receptor, we are studying Fgf gene expression patterns in the cochlea and have identified several candidate ligands, which are also candidate hearing loss genes. To evaluate their function, a summer student will generate compound mutant mice carrying both the mutant receptor and reduced levels of the candidate ligands for assessment of rescue of hearing function. Another possible project is to test the hypothesis that systemic application of chemical inhibitors of the signaling pathway downstream of the activated FGF receptor will rescue cell fate specification and hearing function in mutation carriers. I will be happy to discuss these and other possible projects with any interested students.

12/2007