Duke Regeneration Center and Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Université Côte d'Azur, Inserm, CNRS, Institut de Biologie Valrose, 06100 Nice, France.
Development. 2023 Dec 15;150(24). doi: 10.1242/dev.202076. Epub 2023 Dec 11.
Identification of signaling events that contribute to innate spinal cord regeneration in zebrafish can uncover new targets for modulating injury responses of the mammalian central nervous system. Using a chemical screen, we identify JNK signaling as a necessary regulator of glial cell cycling and tissue bridging during spinal cord regeneration in larval zebrafish. With a kinase translocation reporter, we visualize and quantify JNK signaling dynamics at single-cell resolution in glial cell populations in developing larvae and during injury-induced regeneration. Glial JNK signaling is patterned in time and space during development and regeneration, decreasing globally as the tissue matures and increasing in the rostral cord stump upon transection injury. Thus, dynamic and regional regulation of JNK signaling help to direct glial cell behaviors during innate spinal cord regeneration.
鉴定有助于斑马鱼固有脊髓再生的信号事件,可以揭示调节哺乳动物中枢神经系统损伤反应的新靶点。我们使用化学筛选方法,鉴定出 JNK 信号是幼虫斑马鱼脊髓再生过程中神经胶质细胞周期和组织桥接的必要调节因子。通过激酶易位报告基因,我们在发育中的幼虫和损伤诱导的再生过程中,以单细胞分辨率可视化和定量 JNK 信号在神经胶质细胞群体中的动态。神经胶质 JNK 信号在发育和再生过程中具有时间和空间上的模式,随着组织的成熟而全局降低,并在横断损伤后在脊髓残端的头部增加。因此,JNK 信号的动态和区域调节有助于指导固有脊髓再生过程中的神经胶质细胞行为。