Auditory hair cell regeneration
Hair cells are the sensory receptors of both the auditory and vestibular systems of all vertebrates. Hearing and vestibular impairment can be caused by the loss of these specialized cells. Hair cell loss in humans and other mammals is permanent, but regeneration of lost hair cells occurs spontaneously in non-mammalian vertebrates including fish, amphibians, reptiles, and birds. Understanding the process of hair cell regeneration in non-mammalian vertebrates may lead to the development of important therapeutics and/or preventions for hair cell loss in humans.
The Smith Lab is currently funded by the NIH INBRE Program (IDeA Networks of Biomedical Research Excellence) to examine the process of auditory hair cell regeneration in zebrafish. Julie Schuck examined the timecourse of hair cell regeneration in zebrafish following acoustic trauma and found that there is a peak of cell proliferation in the saccule two days following sound exposure and that it takes approximately two weeks for hair cell densities to return to control levels (Schuck & Smith, 2009). Microarray analysis of zebrafish inner ear tissues at two and four days following acoustic exposure found differential gene expression in hundreds of genes compared to controls, but the gene that was most highly up-regulated two days post-exposure was growth hormone (Schuck et al., 2011). Since then, our lab has focused on the effects of growth hormone on the zebrafish inner ear. We have found that growth hormone injection promotes hair cell regeneration in the zebrafish inner ear following acoustic trauma by increasing cell proliferation and suppressing apoptosis (Sun et al., 2011). We are currently examining the cellular pathways that growth hormone affects during hair cell regeneration using Next-Generation Sequencing technology.
Besides intense acoustic stimuli, hair cells of the zebrafish inner ear can be damaged by ototoxic chemicals such as aminoglycoside antibiotics. Recently, we collaborated with the Jonathan Matsui lab to examine the effects of gentamicin (an aminoglycoside antibiotic) on the zebrafish inner ear. We found that injection of gentamicin caused a reduction in saccular hair cells and increased hearing thresholds (quantified via auditory evoked potential recording; Uribe et al., 2013). In the future, we will examine differences in cell death and regeneration pathways mediated via acoustic trauma and ototoxic chemicals.