Abstract：
In the zebrafish lateral line, non-sensory supporting cells readily re-enter the cell cycle to generate new hair cells and supporting cells during homeostatic maintenance and following damage to hair cells. This contrasts with supporting cells from mammalian vestibular and auditory sensory epithelia which rarely re-enter the cell cycle, and hence loss of hair cells results in permanent sensory deficit. Lateral line supporting cells are derived from multipotent progenitor cells that migrate down the trunk midline as a primordium and are deposited to differentiate into a neuromast. We have found that we can revert zebrafish support cells back to a migratory progenitor state by pharmacologically altering the signaling environment to mimic that of the migratory primordium, with active Wnt signaling and repressed FGF signaling. The reverted supporting cells migrate anteriorly and posteriorly along the horizontal myoseptum and will re-epithelialize to form an increased number of neuromasts along the midline when the pharmacological agents are removed. These data demonstrate that supporting cells can be readily reprogrammed to a migratory multipotent progenitor state that can form new sensory neuromasts, which has important implications for our understanding of how the lateral line system matures and expands in fish and also suggest avenues for returning mammalian supporting cells back to a proliferative state.
摘要：
在斑马鱼侧线，非感觉支持细胞在体内平衡维持和毛细胞受损期间容易重新进入细胞周期以产生新的毛细胞和支持细胞。这与来自哺乳动物前庭和听觉感觉上皮的支持细胞形成对比，这些细胞很少重新进入细胞周期。因此毛细胞的损失导致永久性的感觉缺陷。侧线支持细胞源自多能祖细胞，该多能祖细胞作为原基沿着主干中线迁移并沉积以分化为神经肥大细胞。我们已经发现，我们可以通过药理学改变信号环境来模拟迁移原基，使斑马鱼支持细胞恢复到迁移祖细胞状态，与活跃的Wnt信号和抑制的FGF信号。回复的支持细胞沿水平肌间隔向前和向后迁移，并在去除药理剂时沿中线重新上皮形成数量增加的神经柱。这些数据表明，支持细胞可以很容易地重新编程为可形成新的感觉神经腺体的迁移多能祖细胞状态，这对我们了解侧线系统如何在鱼类中成熟和扩展具有重要意义，也为使哺乳动物支持细胞恢复增殖状态提供了途径。
