Activation of Cell Cycle Re-entry in the Mammalian Inner Ear
- Type of resource
- Date created
- April 05, 2018
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Honors theses written by undergraduates in the Stanford University Department of Biology, 2017-18., Honors theses written by undergraduates in the Stanford University Department of Biology, 2017-18., Honors theses written by undergraduates in the Stanford University Department of Biology, 2017-18.
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Hearing loss is the most common sensory deficit in the U.S. The adult mammalian cochlea, specifically the sensory hair cells located in the organ of Corti, lack regenerative capacity, which is the main reason for permanent hearing loss. Broadly, this research considers potential ways to restore hearing through hair cell regeneration, which occurs naturally in lower vertebrates, such as chicken and fish, but not in mammals and humans. More specifically, it tests the hypothesis that forced overexpression of positive cell cycle regulators Cyclin B, Cyclin D, CDK1, and CDK4 is sufficient to induce cell cycle re-entry and will enable proliferative hair cell regeneration in postnatal supporting cells of the organ of Corti. To do this, we virally infected organ of Corti explants from Pou4f3DTR/Fgfr3-iCreERT2/Ai14/Atoh1-nGFP mice. In these mice, DTR (Human Diphtheria Toxin Receptor) is expressed under the hair cell specific Pou4f3 promotor and allows for induced hair cell death upon injection of the toxin. In addition to enabling Pou4f3-mediated hair cell death, the mouse model allows fate tracking of a supporting cell subpopulation by Fgfr3-tdTomato-expression and direct identification of hair cells by Atoh1-nGFP signals. After viral infection, explants were exposed to the thymidine analog EdU, which was used to trace supporting cells that re-entered S-phase and divided in response to viral induction. We found that cochlear supporting cells re-entered the cell cycle, subsequently proceeded to mitosis and successfully completed division. The strategy reported in this study is novel and contributes to the field of induced hair cell regeneration in the organ of Corti.
- Preferred Citation
- Cheng, Melodyanne Y, Heller, Stefan, Red-Horse, Kristy. (2018). Activation of Cell Cycle Re-entry in the Mammalian Inner Ear. Stanford Digital Repository. Available at: https://purl.stanford.edu/fp630bg7282
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