March 17, 2008 – When birds, reptiles, fish, and amphibians lose cells that enable them to hear, they have the enviable capacity to do something people cannot-regenerate those cells and regain their hearing.
University of Utah neurobiologist Tatjana Piotrowski, Ph.D., wants to know why those lower vertebrates (vertebrates are animals with internal bone skeletons and spinal cords) can regenerate hearing cells, called hair cells, while higher vertebrates, including people and all other mammals, can’t regenerate hair cells.
“In chickens, amphibians, reptiles and others, hair cells that die naturally or from injury grow back,” said Piotrowski, assistant professor of neurobiology and anatomy. “The big question is why mammals lost the ability to replace lost hair cells. It makes you think there’s one step in the process that is not occurring properly.”
To search for answers, Piotrowski is studying genetic mutations in zebrafish, a tiny, tropical minnow that has the same hair cells as humans and is a simple and easy model for understanding hair cell regeneration. The National Organization for Hearing Research Foundation (NOHR) has awarded Piotrowski and co-investigator Alejandro Sanchez-Alvarado, Ph.D., professor of neurobiology and anatomy and an investigator with the Howard Hughes Medical Institute, a $200,000, two-year grant for the study.
Hair cells, named for tiny hair-like projections that line the cochlea in the human inner ear, enable people to hear by converting sound into electrical signals, which are deciphered in the brain. But if hair cells become damaged or die through exposure to loud noise, aging or the use of antibiotics-the leading causes of hair cell death-partial or total hearing loss can result.
In zebrafish, hair cells are part of the lateral line, a sensory system on the outside of the skin that detects water motion and allows the fish to discern its environment for eating, sensing water velocity, capturing prey and avoiding predators, and for schooling. The lateral line is made of neuromasts, which are sensory organs that contain hair cells and are deposited along the length of the zebrafish body.
When zebrafish hair cells die, they have neighboring “support cells” that divide into two “daughter” cells. These daughter cells, in turn, eventually become new hair cells to replace the damaged ones. For that to happen, genes in the support cells must be turned on to initiate the process, according to Piotrowski.
“As yet we do not understand which genes are turned on in support cells upon hair cell death,” she said. “We aim to identify these genes in fish with the hope that we will be able to activate these genes in mammals in the future.”
To identify those genes, Piotrowski plans to randomly knock out or disable genes in zebrafish. Fish that can’t regenerate hair cells possess mutations in genes that are important for hair cell regeneration, thereby revealing the nature of these genes. Many genes are likely to interact in hair cell regeneration, but initially Piotrowski will focus on identifying individual genes that affect the process.
“Individual zebrafish mutants are like puzzle pieces, and at the end we’ll have to put the pieces back together,” she said. “What we learn from zebrafish will tell us which genes need to be activated for hair cell regeneration to occur. This knowledge will then allow us to study why hair cells do not regenerate in mammals and, hopefully, will enable us to jumpstart this process in the future.”