Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells
Chen, Y.; Lee, J. H. H.; Li, J.; Park, S.; Perez-Flores, M. C.; Peguero, B.; Kersigo, J.; Kang, M.; Choi, J.; Levine, L.; Gratton, M. A.; Friztsch, B.; Yamoah, E. N.
Show abstract
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 challenging to replace. Here, we show the pharmacogenetic downregulation of Cldn9, a tight junction protein, generates robust supernumerary inner HCs (IHCs) in mice. The ectopic IHC shared functional and synaptic features akin to typical IHCs and were surprisingly and remarkably preserved for at least fifteen months >50% of the mouses life cycle. In vivo, Cldn9 knockdown using shRNA on postnatal days (P) P2-7 yielded analogous functional 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.
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