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成年斑马鱼视网膜再生过程中穆勒胶质细胞和神经祖细胞的特征分析。

Characterization of Müller glia and neuronal progenitors during adult zebrafish retinal regeneration.

作者信息

Thummel Ryan, Kassen Sean C, Enright Jennifer M, Nelson Craig M, Montgomery Jacob E, Hyde David R

机构信息

Department of Biological Sciences and the Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USA.

出版信息

Exp Eye Res. 2008 Nov;87(5):433-44. doi: 10.1016/j.exer.2008.07.009. Epub 2008 Aug 5.

Abstract

The adult zebrafish retina exhibits a robust regenerative response following light-induced photoreceptor cell death. This response is initiated by the Müller glia proliferating in the inner nuclear layer (INL), which gives rise to neuronal progenitor cells that continue to divide and migrate to the outer nuclear layer (ONL), where they differentiate into rod and cone photoreceptors. We previously conducted a microarray analysis of retinal gene expression at 16, 31, 51, 68, and 96 h of constant intense-light treatment to identify genes and their corresponding proteins that may be involved in the generation and proliferation of the neuronal progenitor cells. We examined the expression of two candidate transcription factors, Pax6 and Ngn1, and one candidate transgene, olig2:EGFP, in the regenerating light-damaged retina. We compared the temporal and spatial expression patterns of these markers relative to PCNA (proliferating cell nuclear antigen), an established marker for proliferating cells in the zebrafish retina, and the Tg(gfap:EGFP) nt11 transgenic line that specifically labels Müller glial cells. We found that Müller glial cells dedifferentiate during regeneration, based on the loss of cell-specific markers such as GFAP (glial fibrillary acidic protein) and glutamine synthetase following their reentry into the cell cycle to produce neuronal progenitors. Pax6 expression was first detected in the proliferating neuronal progenitors by 51 h of constant light treatment, which is significantly after the Müller glia first reenter the cell cycle after 31h of light. This suggests that Pax6 expression increases in neuronal progenitors, rather than in the proliferating Müller glia. EGFP expression from the olig2 promoter was first detected by 68 h of constant light treatment in the dedifferentiated Müller glia, with Pax6 expressed in the closely associated proliferating neuronal progenitors migrating to the ONL. Both Pax6 and olig2 expression persisted until 3 days post-light treatment, when the neuronal progenitors begin differentiating into new rod and cone photoreceptors. Ngn1 protein expression was initially detected in proliferating neuronal progenitors at 68 h of light treatment. However, Ngn1 expression persisted in a subset of the INL nuclei until 17 days post-light treatment. Using the Tg(gfap:EGFP) nt11 transgenic line, Ngn1 was localized to the Müller glial nuclei that were reestablished following the regenerative response. These markers, therefore, can be used to identify different cell types at particular stages of retinal regeneration: neuronal progenitor formation, proliferation, and the reestablishment of the Müller glia cells. These markers will be important to further characterize the regeneration response in other retinal damage models and to elucidate the defects associated with mutants and morphants that disrupt the regeneration response.

摘要

成年斑马鱼视网膜在光诱导的光感受器细胞死亡后表现出强大的再生反应。这种反应由在内核层(INL)中增殖的穆勒胶质细胞启动,这些细胞产生神经祖细胞,神经祖细胞继续分裂并迁移到外核层(ONL),在那里它们分化为视杆和视锥光感受器。我们之前对持续强光处理16、31、51、68和96小时后的视网膜基因表达进行了微阵列分析,以鉴定可能参与神经祖细胞生成和增殖的基因及其相应蛋白质。我们检测了再生的光损伤视网膜中两个候选转录因子Pax6和Ngn1以及一个候选转基因olig2:EGFP的表达。我们将这些标记物相对于PCNA(增殖细胞核抗原,斑马鱼视网膜中增殖细胞的既定标记物)以及特异性标记穆勒胶质细胞的Tg(gfap:EGFP) nt11转基因系的时空表达模式进行了比较。我们发现,基于细胞特异性标记物如GFAP(胶质纤维酸性蛋白)和谷氨酰胺合成酶在重新进入细胞周期以产生神经祖细胞后丧失,穆勒胶质细胞在再生过程中去分化。持续光照处理51小时后,在增殖的神经祖细胞中首次检测到Pax6表达,这明显晚于光照31小时后穆勒胶质细胞首次重新进入细胞周期的时间。这表明Pax6在神经祖细胞中表达增加,而不是在增殖的穆勒胶质细胞中表达增加。持续光照处理68小时后,在去分化的穆勒胶质细胞中首次检测到来自olig2启动子的EGFP表达,Pax6在迁移到ONL的紧密相关的增殖神经祖细胞中表达。Pax6和olig2的表达都持续到光照处理后3天,此时神经祖细胞开始分化为新的视杆和视锥光感受器。光照处理68小时后,在增殖的神经祖细胞中最初检测到Ngn1蛋白表达。然而,Ngn1表达在INL细胞核的一个子集中持续到光照处理后17天。使用Tg(gfap:EGFP) nt11转基因系,Ngn1定位于再生反应后重新建立的穆勒胶质细胞核。因此,这些标记物可用于识别视网膜再生特定阶段的不同细胞类型:神经祖细胞形成、增殖以及穆勒胶质细胞的重新建立。这些标记物对于进一步表征其他视网膜损伤模型中的再生反应以及阐明与破坏再生反应的突变体和形态突变体相关的缺陷将非常重要。

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本文引用的文献

2
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Ganglion cell regeneration following whole-retina destruction in zebrafish.
Dev Neurobiol. 2008 Feb 1;68(2):166-81. doi: 10.1002/dneu.20568.
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Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells.
J Neurosci. 2007 Jun 27;27(26):7028-40. doi: 10.1523/JNEUROSCI.1624-07.2007.
7
Mechanisms controlling Pax6 isoform expression in the retina have been conserved between teleosts and mammals.
Dev Biol. 2007 Jul 15;307(2):498-520. doi: 10.1016/j.ydbio.2007.04.015. Epub 2007 Apr 20.
9
Regeneration of inner retinal neurons after intravitreal injection of ouabain in zebrafish.
J Neurosci. 2007 Feb 14;27(7):1712-24. doi: 10.1523/JNEUROSCI.5317-06.2007.
10
Molecular characterization of retinal stem cells and their niches in adult zebrafish.
BMC Dev Biol. 2006 Jul 26;6:36. doi: 10.1186/1471-213X-6-36.

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