Project description:The development of meter-long axons within the nervous system is a remarkable, yet unresolved biological process. The most widely studied aspects of neuronal growth focus on the extension and chemotropism of growth cones. However, over the course of organismal development, short axons elongate up to one meter in length with the systemic expansion of mitotic tissues. The preeminent regulatory mechanism for such synchronized growth between the nervous system and the tissues it spans, is the biomechanical stretch of axons, a known stimulus of axon growth. Here, we reveal the transcriptional profile of stretch-mediated axon growth as found using embryonic rat dorsal root ganglia neurons stretch-grown in vitro.
Project description:Aging-associated inflammatory and oxidative changes in the rat urinary bladder and dorsal root ganglia - preventive effect of caloric restriction [L6 dorsal root ganglia]
Project description:To explored the altered genes during the axon regeneration of rat dorsal root ganglia neurons, we utilized Gene Expression Array to find out the altered expression of genes in cultured DRG neurons at different times. When we digest the cells from rat DRGs with enzymes, we only get the cell bodies of neurons without axons. During the axons re-growth after the neurons planted, it must be amount of genes expression will changed. However, we still not fully understand which genes will changed and the function of these genes. In addition, this cell model could mimic the regeration of sciatic nerve after injure in vivo, which is still a challenge in clinical.
Project description:To explored the function of miRNAs during the axon regeneration of rat dorsal root ganglia neurons, we utilized miRCURYTM LNA Array (v.18.0) to find out the altered expression of miRNAs in cultured DRG neurons at different times. When we digest the cells from rat DRGs with enzymes, we only get the cell bodies without axons. During the axons re-growth after the neurons planted, it must be amount of gene and miRNAs will changed. However, we still not fully understand which miRNAs and mRNA will changed and the function of these miRNAs and mRNAs. In addition, this cell model could mimic the regeration of sciatic nerve after injure in vivo, which is still a challenge in clinical.
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:Nociceptors play an essential role in both acute pain and chronic pain conditions. In this study, we examined the proteome of mouse dorsal root ganglia and compared NaV1.8Cre+/-; ROSA26-flox-stop-flox-DTA (Diphtheria toxin fragment A) mutant mice (NaV1.8Cre-DTA), in which NaV1.8-positive neurons (mainly nociceptors) in dorsal root ganglia (DRG) were ablated, with respective littermate wildtype controls.
Project description:A cGMP signalling cascade composed of the ligand C-type natriuretic peptide (CNP), the natriuretic peptide receptor 2 (Npr2) and the cGMP-dependent kinase Iα (cGKI) is implicated by growth cone splitting in the bifurcation of afferents from dorsal root ganglia (DRG), cranial sensory ganglia (CSG) and mesencephalic trigeminal neurons (MTN). To get further mechanistic insights into the process of axon bifurcation we applied different cell culture approaches to decipher downstream activities of cGKI in somatosensory growth cones. We demonstrate that CNP induces an enlargement of DRG growth cones via cGKI which can be blocked or stimulated by pharmacological reagents that interfere with S-palmitoylation. cGKI colocalizes primarily in the central domain of the growth cone with the palmitoylome and vesicular structures including the endoplasmic reticulum, early endosomes, lysosomes and in the soma in the Golgi apparatus. Consistently, an acyl-biotin-exchange chemistry-based screen indicated that cGMP signalling regulates S-palmitoylation of a restricted pool of proteins in the DRG-derived cell line F11.