Neurobiology and Anatomy

E-mail: piotrowski @neuro.utah.edu
Address: MREB 401
Phone: 587-7638

Identification of genes involved in hair cell regeneration

Deafness is one of the most widespread disabilities in the world. A prominent cause of deafness is loss of hair cells due to age, noise or antibiotic treatments. In mammals degeneration of hair cells is permanent. Thus, there is a need for the development of therapeutic treatment for hearing loss. In contrast to mammalian hair cells, fish, bird and amphibian hair cells turn over frequently during the normal life cycle and regenerate following hair cell death. Little is known why lower vertebrates are able to regenerate hair cells but humans do not. This is partly due to the relative inaccessibility of inner ear hair cells to direct observation and manipulation. We are taking advantage of the lateral line of zebrafish to define and functionally characterize the molecular and cellular interactions occurring during hair cell regeneration. We chose the lateral line of the zebrafish as an experimental paradigm because of 1) its accessibility to direct observation and manipulation throughout development; 2) the functional and morphological similarity between the lateral line hair cells and the hair cells of the inner ear; 3) the transparency of embryos and genetic tools available in zebrafish to molecularly and functionally dissect developmental processes; and 4) the ability of zebrafish support cells to regenerate hair cells. The most important advantage of zebrafish as a model system is that we can rapidly and cost-effectively isolate specific cell types involved in hair cell regeneration, experiments that are difficult to perform in the classical model systems, e.g., mouse and chick. We have performed microarray analyses to identify the earliest genes involved in regeneration. A possible project in the lab for a Medical student would be to functionally analyze candidate genes identified. These experiments will involve in situ hybridization analyses in regenerating and control embryos at different stages, morpholino experiments with these genes and transplantation experiments. The genes identified are likely to be key players in regeneration and will provide us with new insights in the development and regeneration of sensory organs. These results will set the stage for mechanistic studies aimed at developing methods to regenerate hair cells in mammals.

1/2008