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The effect of extrinsic Wnt/β-catenin signaling in Muller glia on retinal ganglion cell neurite growth.
Developmental Neurobiology ( IF 3 ) Pub Date : 2020-04-17 , DOI: 10.1002/dneu.22741
Ganeswara Rao Musada 1 , Galina Dvoriantchikova 1 , Ciara Myer 1 , Dmitry Ivanov 1 , Sanjoy K Bhattacharya 1 , Abigail S Hackam 1
Affiliation  

Muller glia are the predominant glial cell type in the retina, and they structurally and metabolically support retinal neurons. Wnt/β‐catenin signaling pathways play essential roles in the central nervous system, including glial and neuronal differentiation, axonal growth, and neuronal regeneration. We previously demonstrated that Wnt signaling activation in retinal ganglion cells (RGC) induces axonal regeneration after injury. However, whether Wnt signaling within the adjacent Muller glia plays an axongenic role is not known. In this study, we characterized the effect of Wnt signaling in Muller glia on RGC neurite growth. Primary Muller glia and RGC cells were grown in transwell co‐cultures and adenoviral constructs driving Wnt regulatory genes were used to activate and inhibit Wnt signaling specifically in primary Muller glia. Our results demonstrated that activation of Wnt signaling in Muller glia significantly increased RGC average neurite length and branch site number. In addition, the secretome of Muller glia after induction or inhibition of Wnt signaling was characterized using protein profiling of conditioned media by Q Exactive mass spectrometry. The Muller glia secretome after activation of Wnt signaling had distinct and more numerous proteins involved in regulation of axon extension, axon projection and cell adhesion. Furthermore, we showed highly redundant expression of Wnt signaling ligands in Muller glia and Frizzled receptors in RGCs and Muller glia. Therefore, this study provides new information about potential neurite growth promoting molecules in the Muller glia secretome, and identified Wnt‐dependent target proteins that may mediate the axonal growth.

中文翻译:

Muller胶质细胞外源性Wnt /β-catenin信号传导对视网膜神经节细胞神经突生长的影响。

穆勒胶质细胞是视网膜中主要的神经胶质细胞类型,它们在结构和代谢上支持视网膜神经元。Wnt /β-catenin信号通路在中枢神经系统中起着重要作用,包括神经胶质和神经元分化,轴突生长和神经元再生。我们先前证明视网膜神经节细胞(RGC)中的Wnt信号激活可在损伤后诱导轴突再生。但是,未知在相邻的穆勒神经胶质细胞内的Wnt信号是否起着促轴突作用。在这项研究中,我们表征了穆勒胶质细胞中Wnt信号传导对RGC神经突生长的影响。Muller原代胶质细胞和RGC细胞在跨孔共培养物中生长,驱动Wnt调控基因的腺病毒构建体被用于激活和抑制Wnt信号,特别是在Muller原胶质细胞中。我们的结果表明,Muller胶质细胞中Wnt信号的激活显着增加了RGC平均神经突长度和分支部位数量。此外,通过Q Exactive质谱分析条件培养基的蛋白谱,表征了诱导或抑制Wnt信号后Muller胶质细胞的分泌。Wnt信号激活后,Muller胶质细胞分泌蛋白质组具有独特且数量更多的蛋白质,参与调节轴突延伸,轴突投射和细胞粘附。此外,我们在穆勒神经胶质细胞中显示了Wnt信号配体的高度冗余表达,在RGC和穆勒神经胶质细胞中显示了卷曲的受体。因此,这项研究提供了有关Muller胶质细胞分泌物中潜在的神经突生长促进分子的新信息,并鉴定了可能介导轴突生长的Wnt依赖性靶蛋白。
更新日期:2020-04-17
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