This article appeared on OBERLIN ONLINE - June 9, 2003
  Today's Research May Restore Hearing Tomorrow

by Lynne Bianchi
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  JUNE 9, 2003--How does looking at cultured cells in a dish tell us about what goes on in the body? For the past 14 years, my research--and more recently, that of my students--has focused on the formation of the inner ear. More specifically, we have focused on understanding how the nerve fibers (the "wires") that connect the ear to the brain grow and connect to the cells in the inner ear. The inner ear is responsible for conveying information about sound and balance to the brain. The coiled, snail-like region of the inner ear (the cochlea) transmits auditory information, while the looped, semicircular canal regions convey balance (or vestibular) information. The entire inner ear is encased in bone, which protects the region's delicate structures. This makes accessing the inner ear difficult for scientists, whose research is further complicated by the inner ear's tiny size--in an adult, the inner ear is only the size of the tip of a pinky finger. Both the cochlear and vestibular regions contain specialized hair cells that connect to the nerve fibers of the eighth cranial nerve. These nerve cells convey sound and balance information to the brain. Surrounding the hair cells are various supporting cells. These cells do not connect to the nerve fibers, but are nonetheless important in maintaining proper structure and function within the inner ear. Both the hair cells and the supporting cells are arranged in very precise patterns, with the hair cells separated from one another by the supporting cells. How these precise arrangements occur during the cells' development is not fully understood, nor do we know how the nerve fibers initially establish connections with the developing hair cells. One way to address these questions--and gain better access to the inner ear tissues--is to place them into cell culture dishes. This allows scientists to manipulate the cells and test mechanisms that are used for patterning the inner ear cells and establishing nerve fiber connections. My students and I have used tissue culture experiments to test how the development of the inner ear influences the growth of nerve cells. When the auditory and vestibular nerve cells first form, they do not have the nerve fibers that ultimately will connect the inner ear cells to the brain. Instead, the nerve cells grow long fibers that reach toward the developing hair cells in the inner ear. In other systems, the target tissue--or, the tissue that the nerves contact--secretes growth factors that promote the extension of nerve fibers. Our early studies showed that when we placed embryonic inner ear tissue into a dish with embryonic auditory and vestibular nerve cells, the cells began to extend these fibers. However, the cultures that contained only nerve cells, without inner ear tissue, did not extend nerve fibers; only the inner ear tissue could promote the growth of auditory and vestibular nerve fibers. This suggested that the embryonic inner ear secreted a growth factor that caused the extension of auditory and vestibular nerve fibers during the inner ear's developmental phase. My students and I spent several years characterizing this growth factor, but we were unable to identify it. We did experiments in which we added specific growth factors to the cultures of auditory and vestibular nerve fibers, but none of the factors caused the outgrowth of auditory or vestibular nerve fibers. Recently, we have begun to work with Dr. Kate Barald at the University of Michigan, a collaboration that is supported in part by the Oberlin-Kalamazoo/University of Michigan exchange program. Barald's lab has also generated inner ear cell lines that secrete proteins, some of which secrete factors that promote the growth of auditory and vestibular nerve fibers. Because the cell lines produce much more of the growth factor than the embryonic inner ear does, we can use the cell lines for biochemical analysis. One day this analysis will help determine the exact nature of the mysterious inner ear factor that causes nerve fibers to grow. Throughout the years, my students and I have made several other discoveries. For example, by examining the inner ears of mice that lacked the gene for a particular growth factor, we discovered that this factor was important to the survival of auditory and vestibular nerve fibers during mid-embryogeneis. These mice proved that the results we obtained from experiments in a culture dish were similar to what happens in an intact animal. Such results reinforce the advantages of both methods and demonstrate why cell culture and animal experiments are both important methods in the scientific community. In graduate school, when I first started using cell cultures, my friends wondered how using cultured cells could tell me anything about an organism's ability to hear. The cells in my culture dish do not hear, but that's okay. The information we glean from these experiments helps us to understand how the inner ear develops normally. One day, this will help us develop processes that will restore hearing in humans.