Browsing by Author "Peguero, Braulio"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells
    (bioRxiv, 2023-10-10) Chen, Yingying; Lee, Jeong Han; Li, Jin; Park, Seojin; Perez Flores, Maria C.; Peguero, Braulio; Kersigo, Jennifer; Kang, Mincheol; Choi, Jinsil; Levine, Lauren; Gratton, Michael Anne; Fritzsch, Bernd; Yamoah, Ebenezer N.; Pharmacology and Toxicology, School of Medicine
    Hearing loss is the most common form of sensory deficit. It occurs predominantly due to hair cell (HC) loss. Mammalian HCs are terminally differentiated by birth, making HC loss incurable. Here, we show the pharmacogenetic downregulation of Cldn9, a tight junction protein, generates robust supernumerary inner HCs (IHCs) in mice. The putative ectopic IHCs have functional and synaptic features akin to typical IHCs and were surprisingly and remarkably preserved for at least fifteen months >50% of the mouse's life cycle. In vivo, Cldn9 knockdown using shRNA on postnatal days (P) P1-7 yielded analogous functional putative ectopic IHCs that were equally durably conserved. The findings suggest that Cldn9 levels coordinate embryonic and postnatal HC differentiation, making it a viable target for altering IHC development pre- and post-terminal differentiation.