Fibroblast Growth Factor Expression in Inner Correlates with Defects in the Null Mutant

Abstract

The inner ear is a multifunctional organ required for hearing, balance, and proprioception of the head. Each area of sensory cells in the ear must develop to be perfectly situated to receive specific stimulation. Formally, the development of the inner ear can be divided into three components: cell fate assignment, morphogenesis, and proliferation. Cell fate assignment is highly conserved throughout evolution and the same genes are utilized for this task both in mice and insects. In contrast, morphogenesis is poorly conserved evolutionarily, utilizing unique genes or unique gene combinations in higher organisms.|The insect gene corresponding to the fibroblast growth factors (FGFs) does not appear in insect mechanosensor development. However, several of the greatly expanded, 24 member, mammalian FGF family of genes are expressed during the development of the inner ear. Therefore, these genes are considered to appear late in the evolution of the ear and expected to participate in morphogenesis.|FGFs are crucial for branching of the limbs and lungs in mice. Expression patterns in the development of these structures can be used as a model for expression in the ear since many of the same genes are utilized in both budding morphogenesis and ear formation.|The expression pattern of FGF3, 8, 9, and 10 were analyzed in the inner ear. FGF10 has a very stable expression pattern in the sensory epithelia, particularly in the canals, and in the VIIIth ganglion. From this data, FGF10 involvement is expected in the development of the canals and sensory epithelia but its specific activities cannot be determined by expression pattern alone.|Amgen produced mice that do not express FGF10, and they reported the lack of limbs and lungs in these FGF10 null mutants. This lack of budding morphogenesis makes .it impossible to evaluate the loss of gene expression on these structures. However, the mutants do form ears and the malformations in theses ears can be correlated with the FGF10 expression in the normal ear. In the inner ear of the FGF10 null mutants the canals are truncated and the orientation of the canals and the sensory epithelia are dramatically altered. Furthermore, the posterior vertical canal appears to be missing entirely. These data, in addition to FGF10 expression data, imply that E'GFIO is critical for defining polarity of the inner ear on both a global and local scale.