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Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury.

ABSTRACT: Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury.

PROVIDER: PRJNA950032 | ENA |

REPOSITORIES: ENA

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Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury [bulk RNA-seq]

Project description: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.

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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]

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Upregulation of developmentally-downregulated miR-1247-5p promotes neuroprotection and axon regeneration in vivo [RNA-seq]

Project description:Numerous micro-RNAs (miRNAs) affect neurodevelopment and neuroprotection, but potential roles of many miRNAs in regulating these processes are still unknown. Here, we used the retinal ganglion cell (RGC) central nervous system (CNS) projection neuron and optic nerve crush (ONC) injury model, to optimize a mature miRNA arm-specific quantification method for characterizing the developmental regulation of miR-1247-5p in RGCs, investigated whether injury affects its expression, and tested whether upregulating miR-1247-5p-mimic in RGCs promotes neuroprotection and axon regeneration. We found that, miR-1247-5p is developmentally-downregulated in RGCs, and is also further downregulated after ONC. Importantly, RGC-specific upregulation of miR-1247-5p promoted neuroprotection and axon regeneration after injury in vivo. To gain insight into the underlying mechanisms, we analyzed by bulk-mRNA-seq embryonic and adult RGCs, along with adult RGCs transduced by miR-1247-5p-expressing viral vector, and identified developmentally-regulated cilial and mitochondrial biological processes, which were reinstated to their embryonic levels in adult RGCs by upregulation of miR-1247-5p. Because axon growth is also a developmentally-regulated process, in which mitochondrial dynamics play important roles, it is possible that miR-1247-5p promoted neuroprotection and axon regeneration through regulating mitochondrial functions.

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Upregulation of developmentally-downregulated miR-1247-5p promotes neuroprotection and axon regeneration in vivo [Small-RNA-seq]

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Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury [bulk RNA-seq]

Project description:Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury [bulk RNA-seq]

| PRJNA950035 | ENA

Experimental upregulation of developmentally downregulated ribosomal protein large subunits 7 and 7A promotes axon regeneration after injury in vivo [scRNA-Seq]

Project description:Ribosomal proteins are involved in neurodevelopment and central nervous system (CNS) disease and injury. However, the roles of specific ribosomal protein subunits in developmental axon growth, and their potential as therapeutic targets for treating CNS injuries, are still poorly understood. Here, we show that ribosomal protein large (Rpl) and small (Rps) subunit genes are substantially (56-fold) enriched amongst the genes, which are downregulated during maturation of retinal ganglion cell (RGC) CNS projection neuron. We also show that RGC subtype-specific Rpl and Rps subunits are highly co-regulated, and partially re-upregulated after optic nerve crush (ONC). Because developmental downregulation of ribosomal proteins coincides with developmental decline in neuronal intrinsic axon growth capacity, we hypothesized that Rpl/Rps incomplete re-upregulation after injury may be a part of the cellular response which attempts to reactivate intrinsic axon growth mechanism. We found that experimentally upregulating Rpl7 and Rpl7A promoted axon regeneration after ONC in vivo. Finally, we characterized gene networks associated with Rpl/Rps, and showed that Rpl7 and Rpl7A belong to the cluster of genes, which are shared between translational and neurodevelopmental biological processes (based on gene-ontology) that are co-downregulated in maturing RGC during the decline in intrinsic axon growth capacity.

2023-08-28 | GSE240316 | GEO

Single nuclei RNA-seq analysis of control and Dnmt3a conditional knockout (cKO) of retinal ganglion cells at 2 days post optic nerve crush.

Project description:Dnmt3a deficiency in retinal ganglion cells promotes axon regeneration in an optic nerve crush mouse model. To investigate the role of Dnmt3a in axon regeneration, retinal ganglion cell nuclei were sorted from control and retinal ganglion cell-specific Dnmt3a knockout mice at 2 days post optic nerve crush and applied for single nuclei RNA-seq analysis by 10X Genomics technology.

2023-12-14 | GSE228627 | GEO

Experimental upregulation of developmentally downregulated ribosomal protein large subunits 7 and 7A promotes axon regeneration after injury in vivo [bulk RNA-Seq]

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Transcriptional profiling of adult retinal ganglion cells during optic nerve regeneration

Project description:Objective: To identify genes that are differentially expressed in retinal ganglion cells undergoing axon regeneration after optic nerve injury. Adult mice that express cyan-fluorescent protein (CFP) in RGCs were treated with pro-regenerative treatment after optic nerve injury. The treated RGCs were selected by FACS (CFP+mcherry) and their RNA profiles were analyzed.

2020-12-29 | GSE142881 | GEO

Bulk RNA-seq analysis of control and Dnmt3a conditional knockout (cKO) retinal ganglion cells at 2 days post optic nerve crush

Project description:Dnmt3a deficiency in retinal ganglion cells promotes axon regeneration in an optic nerve crush mouse model. To investigate the role of Dnmt3a in axon regeneration, retinal ganglion cells isolated from control and retinal ganglion cell-specific Dnmt3a knockout mice at 2 days post-crush were applied for Bulk RNA-seq analysis by NovaSeq platform.

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