Hearing and balance in mammals depends upon proper formation and function of the inner ear. The fibroblast growth factor (FGF) family of peptide growth factors play critical roles in otic induction and morphogenesis. Notably, the related factors FGF10 and FGF3 have overlapping roles in ear induction and morphogenesis. Both are expressed in ear-inducing tissues and are required for initial production of an otic vesicle and both are subsequently expressed in dynamic spatio-temporal patterns within the otic vesicle. In this project the principal investigator aims to dissect some of the complex overlapping functions of FGF signaling in the inner ear, to help place Fgf10 within the network of genes governing inner ear development and homeostasis. The principal investigator has located cis-regulatory elements of the Fgf10 gene responsible for otic-region Fgf10 expression, DNA elements that are key molecular components of the genetic program of inner ear development. The project involves delimiting these elements to define the minimal sequences required for their function, a step towards identifying pathways acting upstream of Fgf10. To help dissect the multiple FGFsignals operating in the ear the Fgf10 regulatory elements will also be coupled to Cre recombinase in transgenic mice. These transgenics then will be combined with conditional FGF3/ FGF10 alleles to eliminate FGF3/FGF10 function in a subset of their normal expression patterns. This will allow the morphological and functional consequences of interfering in specific FGF signals to be defined.
