Todd Levi, Squires Natalie, Suarez Lilianna, Fischer Andy J
Department of Neuroscience, College of Medicine, The Ohio State University, 4190 Graves Hall, 333 West 10th Ave, Columbus, OH 43210, USA.
Sci Rep. 2016 Oct 19;6:35703. doi: 10.1038/srep35703.
Müller glia are capable of de-differentiating and proliferating to become Müller glia-derived progenitor cells (MGPCs) with the ability to regenerate retinal neurons. One of the cell-signaling pathways that drives the reprogramming of Müller glia into MGPCs in the zebrafish retina is the Jak/Stat-pathway. However, nothing is known about the influence of Jak/Stat-signaling during the formation of MGPCs in the retinas of warm-blooded vertebrates. Accordingly, we examined whether Jak/Stat-signaling influences the formation of MGPCs and differentiation of progeny in the avian retina. We found that Jak/Stat-signaling is activated in Müller glia in response to NMDA-induced retinal damage or by CNTF or FGF2 in the absence of retinal damage. Inhibition of gp130, Jak2, or Stat3 suppressed the formation of proliferating MGPCs in NMDA-damaged and FGF2-treated retinas. Additionally, CNTF combined with FGF2 enhanced the formation of proliferating MGPCs in the absence of retinal damage. In contrast to the zebrafish model, where activation of gp130/Jak/Stat is sufficient to drive neural regeneration from MGPCs, signaling through gp130 inhibits the neurogenic potential of MGPCs and promotes glial differentiation. We conclude that gp130/Jak/Stat-signaling plays an important role in the network of pathways that drives the formation of proliferating MGPCs; however, this pathway inhibits the neural differentiation of the progeny.
穆勒胶质细胞能够去分化并增殖，成为具有再生视网膜神经元能力的穆勒胶质细胞衍生祖细胞（MGPCs）。在斑马鱼视网膜中，驱动穆勒胶质细胞重编程为MGPCs的细胞信号通路之一是Jak/Stat通路。然而，关于Jak/Stat信号在温血脊椎动物视网膜中MGPCs形成过程中的影响，我们一无所知。因此，我们研究了Jak/Stat信号是否会影响禽类视网膜中MGPCs的形成以及子代的分化。我们发现，在NMDA诱导的视网膜损伤后，或在无视网膜损伤的情况下，由睫状神经营养因子（CNTF）或成纤维细胞生长因子2（FGF2）作用时，穆勒胶质细胞中的Jak/Stat信号会被激活。抑制gp130、Jak2或Stat3会抑制NMDA损伤和FGF2处理的视网膜中增殖性MGPCs的形成。此外，在无视网膜损伤的情况下，CNTF与FGF2联合使用可增强增殖性MGPCs的形成。与斑马鱼模型不同，在斑马鱼模型中，gp130/Jak/Stat的激活足以驱动MGPCs的神经再生，而通过gp130的信号传导会抑制MGPCs的神经发生潜能并促进胶质细胞分化。我们得出结论，gp130/Jak/Stat信号在驱动增殖性MGPCs形成的信号通路网络中起重要作用；然而，该通路会抑制子代的神经分化。
