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An In Vivo Method for Ablating Hair Cells in order to Study Regeneration in the Ear

Presenters Name: 
Bailey Moskowitz
Primary Research Mentor: 
Jeffrey Corwin
Secondary Research Mentor: 
Mark Rudolf
2:15 - 2:30
Time of Presentation: 
2019 - 2:15pm to 2:30pm
South Meeting Room
Presentation Type: 
Presentations Academic Category: 
Grant Program Recipient: 
Not a Recipient

Throughout life, the ears of birds, fish, and amphibians can regenerate sensory hair cells and recover after deafening, yet the ears of humans and other mammals lose the capacity for regeneration during embryogenesis or soon thereafter. The development of therapies to restore hearing and balance function will depend on understanding the mechanisms that underlie such repair. As a test to determine whether hair cell loss activates YAP1, a protein that promotes proliferation in the developing ear we used the compound 3,3’-iminodipropionitrile (IDPN) to ablate hair cells in mice. We hypothesized that hair cell loss in young mice would induce the accumulation of YAP1 in cell nuclei, a sign of YAP1 activation. To test this, we injected eight five-day-old mice with 2 mg/g IDPN, and another eight littermates with saline. After four days, we harvested, fixed, and imaged their utricles (a balance organ), quantified their hair cells and measured the nuclear:cytoplasmic ratio of YAP1 in the supporting (stem) cells. The hair cell density was significantly lower in utricles of IDPN-treated mice compared to saline-injected controls (69±22 vs 173±35 cells per 10,000 µm2), indicating that IDPN had killed hair cells. Supporting cells in damaged utricles had significantly higher nuclear:cytoplasmic ratios of YAP1 than those in controls (1.23±0.26 vs 0.89±0.06). We conclude that IDPN-mediated hair cell loss induces activation of YAP1 in neonatal mice. We are currently testing one-month-old mice to determine whether this putative regenerative response persists in the ears of older mammals.