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
University of Nevada, Reno, School of Medicine, Department of Physiology and Cell Biology, Reno NV 89557.
Indiana University School of Medicine, Department of Pharmacology and Toxicology, Indianapolis, IN, 46202, USA.
bioRxiv. 2024 Nov 8:2023.10.08.561387. doi: 10.1101/2023.10.08.561387.
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 , 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 mouse's life cycle. , 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.
听力损失是最常见的感觉缺陷形式。它主要是由于毛细胞（HC）损失而发生。哺乳动物的毛细胞在出生时就已终末分化，使得毛细胞损失后难以替换。在这里，我们表明紧密连接蛋白的药物遗传学下调在小鼠中产生了大量强健的额外内毛细胞（IHC）。异位内毛细胞具有与典型内毛细胞相似的功能和突触特征，令人惊讶的是，在小鼠生命周期的至少15个月（超过50%）内它们被显著保留。在出生后第（P）2 - 7天使用短发夹RNA（shRNA）敲低 ，产生了类似的功能性异位内毛细胞，它们同样被持久保存。这些发现表明，Claudin 9水平协调胚胎期和出生后毛细胞的分化，使其成为在终末分化前后改变内毛细胞发育的一个可行靶点。
