Project description:To study the gene expression at the level of dorsal root ganglia and spinal cord in acute herpetic neuralgia mice, we induced acute herpetic neuralgia by subcutaneous injection of HSV-1 virus fluid into the tibia of C57/6J mice. We collected data obtained from RNA-seq of dorsal root ganglia and spinal cord tissue in acute herpetic neuralgia mice (7 days after virus injection) and control mice for gene expression profiling.
Project description:We demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development.
Project description:Purpose: Nerve injury-induced hyperactivity of primary sensory neurons in the dorsal root ganglion (DRG) contributes critically to chronic pain development, but its underlying mechanisms remain incompletely understood. Chronic neuropathic pain has a clear epigenetic component, however, most studies so far have focused on histone modifications. We determined changes of DNA methylation in the rat DRG, spinal cord, and prefrontal cortex after spinal nerve ligation (SNL).
Project description:Purpose: Nerve injury-induced hyperactivity of primary sensory neurons in the dorsal root ganglion (DRG) contributes critically to chronic pain development, but its underlying mechanisms remain incompletely understood. Chronic neuropathic pain has a clear epigenetic component, however, most studies so far have focused on histone modifications. We determined changes of DNA methylation in the rat DRG, spinal cord, and prefrontal cortex after spinal nerve ligation (SNL).
Project description:We demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development. in total 6 probes: 3 replica of TNC_wt and 3 replica of TNC_ko
Project description:The goal of this study was to compare the transcriptional effects of sciatic nerve injury and spinal cord injury on lumbar dorsal root ganglion (DRG) and FACS-sorted dorsal column (DC) sensory neurons. We performed RNA-seq of whole DRG from naïve and spinal cord-injured (SCI) mice (1dpi) and compared this with previously published data for sciatic nerve transection. In order to assess changes specifically in DC neurons, we performed RNA-seq from FACS-sorted DC neurons from Thy1-YFP16 transgenic mice in naïve, sciatic nerve injured (SNI), and SCI (1 and 3dpi). We found that DC neurons alter their transcriptome after SCI, but that gene changes after SCI mostly differ from SNI. These transcriptional differences may reflect both growth promoting and growth inhibitory effects on axon regeneration after SCI.
Project description:Expression profiling of L4 and L5 Dorsal Root Ganglion (DRG) in the spinal nerve ligation model of neuropathic pain. The goal of the study was to identify genes involved in neuropathic pain
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.
Project description:Our study examined a population of radial glial-like cells (RGLCs) in the dorsal spinal cord midline that we showed provide long-distance growth support for longitudinal rapidly adapting (RA) mechanoreceptor axons during development of spinal cord dorsal column. To evaluate potential molecular markers of these cells, we isolated the RGLCs using hematoxylin and eosin staining to visualize the cell bodies in the dorsal column midline from E14.5 mouse embryos, and used laser capture microdissection for each sample ("LCM"). To compare transcript expression to the adjacent RA mechanoreceptive axons, we performed FACS of dorsal root ganglion of E14.5 Ret-Tdtomato+ RA mechanoreceptors. Our analyses revealed a high enrichment of radial glial-specific markers in the LCM replicates compared to Ret-Tdt samples. In contrast, neuronal-specific markers were more highly enriched in the Ret-Tdt samples, as expected. These data suggest the midline RGLCs are of radial glial identity. Others may find these data helpful in determining potential RGLC-mechanoreceptor molecular interactions in subsequent studies.