Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury [third-party re-analysis]

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) axons in vivo are 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 injury in 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. Normalized matrices and cell metadata (e.g., type assignment) for embryonic, adult uninjured, and adult injured RGCs, are available from the GEO accession numbers GSE122466 and GSE137400. Postnatal RGC scRNA-seq dataset we previously generated is available under the Gene Expression Omnibus (GEO) accession number GSE115404. data processing step: Cell-counts matrices were obtained from the GEO submissions from the previously published data. Matrices were loaded as seurat objects in R. Seurat objects were merged and expression was normalized. A cell counts matrix for the merged dataset was then generating by extracting counts matrix from seurat object. The condition each cell belongs to was appended to the cell ID in the columns of the matrix genome build/assembly: mm10 processed data files format and content: One CSV files: Containg RGC embyonic, postnatal, adult and injured cells' normalized expression values for each gene.