Megerson Ellen, Kuehn Michael, Leifer Ben, Bell Jon, McGraw Hillary F
bioRxiv. 2023 Jul 28:2023.07.27.550825. doi: 10.1101/2023.07.27.550825.
Mechanosensory hair cells in the inner ear mediate the sensations of hearing and balance, and in a specialize lateral line sensory system of aquatic vertebrates, the sensation of water movement. In mammals, hair cells lack the ability of regenerate following damage, resulting in sensory deficits. In contrast, non-mammalian vertebrates, such zebrafish, can renew hair cells throughout the life of the animal. 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 has not been established. We use a zebrafish mutant line, to show that when Wnt signaling is overactivated in the lateral line, excessive regeneration occurs in the absence of increased proliferation, due to an increase in support cells. This contrasts with the previously described role of Wnt signaling during hair cell regeneration. This work will allow 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，在水生脊椎动物特有的侧线感觉系统中，介导水运动的感觉。在哺乳动物中，毛细胞受损后缺乏再生能力，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信号传导是内耳和侧线毛细胞发育所必需的，并调节再生。Kremen1抑制Wnt信号传导和毛细胞形成，尽管其在再生中的作用尚未明确。我们使用一个斑马鱼突变系来表明，当侧线中的Wnt信号过度激活时，在没有增殖增加的情况下会发生过度再生，这是由于支持细胞增加所致。这与之前描述的Wnt信号在毛细胞再生中的作用形成对比。这项工作将使我们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。
