Megerson Ellen, Kuehn Michael, Leifer Ben, Bell Jon M, Snyder Julia L, McGraw Hillary F
Division of Biological and Biomedical Systems, School of Science and Engineering, University of Missouri-Kansas City, Kansas City, MO 64110, USA.
Integrated DNA Technologies, Inc, Coralville, IA 52241, USA.
iScience. 2023 Dec 7;27(1):108678. doi: 10.1016/j.isci.2023.108678. eCollection 2024 Jan 19.
Mechanosensory hair cells in the inner ear mediate the sensations of hearing and balance, and in the specialized lateral line sensory system of aquatic vertebrates, the sensation of water movement. In mammals, hair cells lack the ability to regenerate following damage, resulting in sensory deficits. In contrast, non-mammalian vertebrates, such as zebrafish, can renew hair cells throughout their lifespan. Wnt signaling is required for development of inner ear and lateral line hair cells and regulates regeneration. Kremen1 inhibits Wnt signaling and hair cell formation, though its role in regeneration is unknown. We used a zebrafish mutant line to show overactive Wnt signaling results in supernumerary support cells and hair cell regeneration without increased proliferation, in contrast with the previously described role of Wnt signaling during hair cell regeneration. This work allows us to understand the biology of mechanosensory hair cells and how regeneration might be promoted following damage.
内耳中的机械感觉毛细胞介导听觉和平衡感觉，而在水生脊椎动物特有的侧线感觉系统中，毛细胞介导水运动感觉。在哺乳动物中，毛细胞受损后缺乏再生能力，从而导致感觉缺陷。相比之下，非哺乳动物脊椎动物，如斑马鱼，在其整个生命周期中都能更新毛细胞。Wnt信号通路是内耳和侧线毛细胞发育所必需的，并调节再生过程。Kremen1抑制Wnt信号通路和毛细胞形成，但其在再生中的作用尚不清楚。我们使用一个斑马鱼突变系来表明，与先前描述的Wnt信号通路在毛细胞再生中的作用相反，过度活跃的Wnt信号通路会导致多余的支持细胞和毛细胞再生，且增殖并未增加。这项工作使我们能够了解机械感觉毛细胞的生物学特性，以及损伤后如何促进再生。
