Lisa D. Urness, Ph.D.

The Research

University of Utah

FGF-regulated hearing loss genes: fast-tracking to functional analysis

With the myriad roles of fibroblast growth factors (FGFs) in multiple stages of ear development, it is not surprising that some human hearing loss syndromes are caused by mutations affecting FGFs and their receptors. However, little is known about the genes that are controlled by FGFs. Because FGF signals are reused during later stages of otic innervation, morphogenesis, and sensory cell differentiation, the FGF target genes we identify during placodogenesis may also be targets of later FGF signaling events and could provide many new candidates for hearing and/or balance disorders, thereby impacting diagnosis. Importantly, elucidating the functions of these genes may suggest potential therapeutic interventions. FGFs are required to initiate otic development and are subsequently reused during morphogenesis and sensory development. Our long-term objective is to identify FGF effector genes and to determine their function and relevance to human deafness by analyzing mouse mutants. Specifically, we propose to isolate RNA from pre-otic ectoderm of control and FGF-deficient embryos and perform an expression profiling experiment utilizing a “gene-trap microarray.” This will identify embryonic stem cell lines that carry mutations in FGF target genes. Selected cell lines will be used to generate the corresponding mutant mouse strains for functional studies of hearing and balance.