Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury.
Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury.
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发育下调 Crmp1、Crmp4 和 Crmp5 的实验基因表达可促进视神经损伤后轴突再生和视网膜神经节细胞存活。
DOI：
10.1016/j.brainres.2023.148368
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发表时间：
2023
期刊：
影响因子：
2.9
通讯作者：
Trakhtenberg,EphraimF
中科院分区：
文献类型：
--
作者：
Lukomska,Agnieszka;Theune,WilliamC;Xing,Jian;Frost,MatthewP;Damania,Ashiti;Gupta,Mahit;Trakhtenberg,EphraimF
溃缩蛋白反应介导蛋白（Crmps）在神经元发育和轴突生长中起作用。然而，Crmp1，Crmp4和Crmp5在损伤的中枢神经系统（CNS）轴突体内再生中的神经元特异性作用尚不清楚。在此，我们分析了视网膜神经节细胞（RGCs）中Crmp基因的发育和亚型特异性表达，测试了通过局部眼内AAV 2递送在RGCs中过表达Crmp 1、Crmp 4或Crmp 5是否促进体内视神经损伤后的轴突再生，并表征了与Crmp相关的基因概念网络的发育共调节。我们发现，所有的Crmp基因在成熟过程中的RGCs发育下调。然而，虽然Crmp 1，Crmp 2和Crmp 4在大多数RGC亚型中表达不同程度，但Crmp 3和Crmp 5仅在一小部分RGC亚型中表达。结果发现，视神经损伤后，Crmp 1、Crmp 4和Crmp 5均不同程度地促进RGC轴突再生，其中Crmp 4促进轴突再生最多，且定位于轴突。我们还发现，Crmp1和Crmp4，而不是Crmp5，促进RGC的生存。最后，我们发现Crmp 1、Crmp 2、Crmp 4和Crmp 5促进轴突再生的能力与控制RGC内在轴突生长能力的神经发育机制有关。
Collapsin response mediator proteins (Crmps) play roles in neuronal development and axon growth. However, neuronal-specific roles of Crmp1, Crmp4, and Crmp5 in regeneration of injured central nervous system (CNS) axonsin vivoare unclear. Here, we analyzed developmental and subtype-specific expression of Crmp genes in retinal ganglion cells (RGCs), tested whether overexpressing Crmp1, Crmp4, or Crmp5 in RGCs through localized intralocular AAV2 delivery promotes axon regeneration after optic nerve injuryin vivo, and characterized developmental co-regulation of gene-concept networks associated with Crmps. We found that all Crmp genes are developmentally downregulated in RGCs during maturation. However, while Crmp1, Crmp2, and Crmp4 were expressed to a varying degree in most RGC subtypes, Crmp3 and Crmp5 were expressed only in a small subset of RGC subtypes. We then found that after optic nerve injury, Crmp1, Crmp4, and Crmp5 promote RGC axon regeneration to varying extents, with Crmp4 promoting the most axon regeneration and also localizing to axons. We also found that Crmp1 and Crmp4, but not Crmp5, promote RGC survival. Finally, we found that Crmp1, Crmp2, Crmp4, and Crmp5′s ability to promote axon regeneration is associated with neurodevelopmental mechanisms, which control RGC’s intrinsic axon growth capacity.