Jizhen Lin, Principal Investigator

Biology of Cochlear Hair Cells

Cochlear hair cells are specialized receptor cells for perception of sounds. A battery of transcription factors is involved in the development of hair cells and thousands of their related genes are expressed in this unique cell population, which acts in harmony to transform sound movements into perceivable electrosignals for the auditory cortex. Full knowledge of the genetic programs for cochlear development and a complete repertoire of gene expression in the cochlear hair cells is essential for understanding the generation of hair cells and the intricate and precise processes of hearing. Application of microarray, combined with carrier deoxyribonucleic acid (cDNA) subtraction, may lead to the discovery of genetic programs for hair cell regeneration and the repertoire of genes, known or novel, that direct hearing activity.

This project uses laser capture microdissection (LCM), a tool specifically designed to isolate single cells, to harvest pure cochlear duct and hair cells. After procuring target tissues or cells by LCM, the researchers isolate and amplify their full spectrum of messenger ribonucleic acid (transcriptome) using standard methods. They then profile the expression of transcription factors in cochlear ducts and their downstream molecules in hair cells. The first step is to use microarrays to determine the dynamic expression of transcription factors along the developmental path of hair cells. Next, cell culture systems are used to further characterize these transcription factors and their downstream molecules. Lastly, the researchers use cDNA extraction to identify novel transcription factor genes involved in hair cell development, followed by molecular cloning procedures for appreciation of their functions in hearing. Most, if not all, transcription factor genes involved in hair cell development should be identified through this comprehensive approach.

The central hypothesis of this study is that once the transcription factors for cochlear development and genes for hearing are appreciated, the molecular mechanisms for hair cell generation and hearing will be better understood. This will provide a foundation for rational design of innovative strategies for prevention and treatment of deafness, which affects almost thirty million Americans and costs the U.S. over $56 billion annually.