Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS

ABSTRACT: Purpose: Injuries to the adult central nervous system (CNS) often result in permanent disabilities because neurons lose the ability to regenerate their axon during development. Although the developmental transition from a growing to a transmitting phase may represent one of the first steps in the gradual loss of axon growth and regeneration ability, the molecular mechanisms regulating this process has yet to be identified. The main goal of this study was to dissect the molecular mechanisms mediating the decline in axon growth ability and its relationship with regeneration failure in the adult CNS. To this end, we sequenced the whole transcriptome of dorsal root ganglia (DRG) neurons in both growth competent and incompetent states at different developmental stages, in diverse culture and in vivo experimental conditions.

ORGANISM(S): Mus musculus

PROVIDER: GSE66128 | GEO | 2016/09/17

SECONDARY ACCESSION(S): PRJNA275932

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Overexpression of KLF genes in retinal ganglion cells

Project description:Adult mammalian CNS neurons undergo a developmental switch in intrinsic axon growth ability associated with their failure to regenerate axons after injury. Krüppel-like transcription factors (KLF) regulate intrinsic axon growth ability, but signaling regulation upstream and downstream is poorly understood. Here we find that suppressing expression of KLF9, an axon growth suppressor normally upregulated 250-fold in retinal ganglion cell (RGC) development, promotes long-distance optic nerve regeneration in vivo. We identify a novel binding partner, MAPK10/JNK3, critical for KLF9’s axon growth suppressive activity. Additionally, by screening genes regulated by KLFs in RGCs, we identify dual-specificity phosphatase 14 (Dusp14) as key to limiting axon growth and regenerative ability downstream of KLF9, associated with its dephosphorylation of MAPKs critical to neurotrophic signaling of RGC axon elongation. These results now link intrinsic and extrinsic regulation of axon growth and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.

2018-06-06 | GSE92507 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RRBS)

Project description:Current treatments for neurodegenerative diseases and neural injuries fall short of success. One primary reason is that neurons in the mammalian central nervous system (CNS) lose their regeneration ability as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulation of mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons to support spontaneous axon regeneration following peripheral nerve injury. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 supported axon regeneration by systematically silencing the transcription of genes regulating synaptic function and inhibiting axon regeneration, while simultaneously activating various axon regeneration promoting factors. In particular, our study demonstrated that the GABA transporter 2 encoded by the gene Slc6a13 acted downstream of Ezh2 to control axon regeneration. Our study suggested that modulating chromatin accessibility was a promising strategy to promote CNS axon regeneration.

2023-12-22 | GSE247319 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq II)

2023-12-22 | GSE247318 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq I)

2023-12-22 | GSE247317 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (ATAC-Seq)

2023-12-22 | GSE247315 | GEO

Robust axonal regeneration occurs in the injured CAST/Ei mouse central nervous system

Project description:Axon regeneration in the central nervous system (CNS) requires reactivating injured neurons’ intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater spouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. These screens are presented here. Biological quadruplicate - Mouse tissue - Naïve Dorsal Root Ganglia (DRG) and 5 day post sciatic nerve crush DRG - x9 strains.

2015-07-22 | E-GEOD-67130 | biostudies-arrayexpress

Genome wide chromatin accessibility analysis reveals a role for CREB in retinal ganglion cells axon growth decline in development and regeneration after optic nerve injury [ATAC-seq]

Project description:CNS neurons lose their ability to grow and regenerate axons during development. This is the case for Retinal Ganglion Cells (RGCs) in the retina, which transmit visual information to the brain via axons projecting into the optic nerve. RGCs are unable to regenerate their axon after injury, and start a degeneration process that leads to cell death and loss of vision. To identifying molecular mechanisms that increase regeneration of RGC and may offer new treatment strategies for patients with glaucoma or other types of optic neuropathies, we focused on the identification of transcription factors and chromatin accessible sites that are enriched in RGC during developmental stages, in which axon growth capacity is robust. We find that stage-specific gene expression changes are correlated with temporal changes in promoter chromatin accessibility. We also find that Creb binding motifs are enriched in the differentially opened regions of the chromatin at embryonic developmental stage. Overexpression of active Creb promotes axon regeneration after optic nerve injury. Our results provide a map of the chromatin accessibility during RGC development and highlights that manipulating TF associated with developmental stages can stimulate axon growth in adulthood.

2021-07-28 | GSE163562 | GEO

Genome wide chromatin accessibility analysis reveals a role for CREB in retinal ganglion cells axon growth decline in development and regeneration after optic nerve injury [RNA-seq]

2021-07-28 | GSE163563 | GEO

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]

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.

2023-04-10 | GSE228486 | GEO

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]

2023-04-10 | GSE228485 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data