Abstract：
Traumatic injury to the spinal cord can lead to significant, permanent disability. Mammalian spinal cords are not capable of regeneration; in contrast, adult zebrafish are capable of such regeneration, fully recovering motor function. Understanding the mechanisms underlying zebrafish neuroregeneration may provide useful information regarding endogenous regenerative potential and aid in the development of therapeutic strategies in humans. DELTEX proteins (DTXs) regulate a variety of cellular processes. However, their role in neural regeneration has not been described. We found that zebrafish dtx2, encoding Deltex E3 ubiquitin ligase 2, is expressed in ependymo-radial glial cells in the adult spinal cord. After spinal cord injury, the heterozygous dtx2 mutant fish motor function recovered quicker than that of the wild-type controls. The mutant fish displayed increased ependymo-radial glial cell proliferation and augmented motor neuron formation. Moreover, her gene expression, downstream of Notch signaling, increased in Dtx2 mutants. Notch signaling inactivation by dominant-negative Rbpj abolished the increased ependymo-radial glia proliferation caused by Dtx2 deficiency. These results indicate that ependymo-radial glial proliferation is induced by Dtx2 deficiency by activating Notch-Rbpj signaling to improve spinal cord regeneration and motor function recovery.
摘要：
脊髓的创伤性损伤可导致显著的,永久性残疾。哺乳动物脊髓不能再生；相反，成年斑马鱼能够再生，完全恢复电机功能。了解斑马鱼神经再生的潜在机制可能提供有关内源性再生潜力的有用信息，并有助于人类治疗策略的发展。DTX调节多种细胞过程。然而,它们在神经再生中的作用尚未被描述。我们发现，编码DeltexE3泛素连接酶2的斑马鱼dtx2在成年脊髓的室管膜-radial神经胶质细胞中表达。脊髓损伤后，杂合dtx2突变体鱼的运动功能恢复比野生型对照更快。突变鱼表现出增加的室管膜-radial神经胶质细胞增殖和增强的运动神经元形成。此外，她的基因表达，陷波信号的下游，在Dtx2突变体中增加。显性阴性Rbpj引起的Notch信号失活消除了Dtx2缺乏引起的室管膜-radial神经胶质细胞增殖增加。这些结果表明，室管膜-radial胶质细胞增殖是由Dtx2缺乏诱导的，通过激活Notch-Rbpj信号来改善脊髓再生和运动功能恢复。
