This research focuses on hair cell regeneration in the inner ear of birds and mammals. Past research has shown that birds have the capacity to regenerate a nearly normal number and pattern of hair cells in the cochlea and vestibular epithelia after otologic trauma. These regenerated hair cells are functional, establish connections with the brain and restore behavioral losses. Mammals show very limited proliferation and no hair cell differentiation and remain hearing- or balance-impaired after similar trauma. This continuation of this research program will attempt to better understand the biological mechanisms underlying this regeneration process in birds by intensive study of the hair cell progenitors in avian and mammalian inner ear tissue. Three approaches to these problems are proposed. One set of experiments will use three-dimensional electron microscopic reconstructions of normal and regenerating sensory epithelium from the cochlea of chicks to examine the variations of sensory epithelium supporting cell morphology and ultrastructure in normal animals as regeneration begins. A second set of experiments will attempt to isolate the hair cell progenitors from the avian cochlea by making culture systems enriched for mitotic cells and then isolating this population into a purified group of regenerative supporting cells. The third group of experiments will use a novel co-culture system to examine the roles of diffusible factors in the regulation of sensory epithelium supporting cell mitotic activity in birds and mammals.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Study Section
Hearing Research Study Section (HAR)
Program Officer
Freeman, Nancy
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University of Washington
Schools of Medicine
United States
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Irvine, Dexter R F; Brown, Mel; Kamke, Marc R et al. (2009) Effects of restricted basilar papillar lesions and hair cell regeneration on auditory forebrain frequency organization in adult European starlings. J Neurosci 29:6871-82
Hirose, Keiko; Westrum, Lesnick E; Cunningham, Dale E et al. (2004) Electron microscopy of degenerative changes in the chick basilar papilla after gentamicin exposure. J Comp Neurol 470:164-80
Cunningham, Lisa L; Matsui, Jonathan I; Warchol, Mark E et al. (2004) Overexpression of Bcl-2 prevents neomycin-induced hair cell death and caspase-9 activation in the adult mouse utricle in vitro. J Neurobiol 60:89-100
Stone, Jennifer S; Shang, Jia Lin; Tomarev, Stanislav (2004) cProx1 immunoreactivity distinguishes progenitor cells and predicts hair cell fate during avian hair cell regeneration. Dev Dyn 230:597-614
Harris, Julie A; Cheng, Alan G; Cunningham, Lisa L et al. (2003) Neomycin-induced hair cell death and rapid regeneration in the lateral line of zebrafish (Danio rerio). J Assoc Res Otolaryngol 4:219-34
Bermingham-McDonogh, Olivia; Rubel, Edwin W (2003) Hair cell regeneration: winging our way towards a sound future. Curr Opin Neurobiol 13:119-26
Stone, Jennifer S; Shang, Jia-Lin; Tomarev, Stanislav (2003) Expression of Prox1 defines regions of the avian otocyst that give rise to sensory or neural cells. J Comp Neurol 460:487-502
Boyle, Richard; Highstein, Stephen M; Carey, John P et al. (2002) Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds. J Assoc Res Otolaryngol 3:149-66
Woolley, Sarah M N; Rubel, Edwin W (2002) Vocal memory and learning in adult Bengalese Finches with regenerated hair cells. J Neurosci 22:7774-87
Cunningham, Lisa L; Cheng, Alan G; Rubel, Edwin W (2002) Caspase activation in hair cells of the mouse utricle exposed to neomycin. J Neurosci 22:8532-40

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