Transcriptional programs controlled by NGF signaling in developing mouse dorsal root ganglia neurons
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE25611 | GEO | 2013/11/01
SECONDARY ACCESSION(S): PRJNA134263
REPOSITORIES: GEO
Similar Datasets
Project description:During embryogenesis, nociceptive sensory neurons of the dorsal root ganglia depend intimately on Nerve Growth Factor (NGF) for neuronal survival, maturation and target innervation. NGF is a secreted molecular signal synthesized by neuronal target tissues. In developing nociceptors, NGF engages the receptor tyrosine kinase TrkA to activate a gene transcriptional program involving the regulation of hundreds of transcripts. To identify NGF-dependent genes in developing mouse nociceptors, we have designed and performed two separate microarray screens to compare gene expression profiles of DRG neurons either with or lacking NGF signaling. For the first screen comparing DRGs of BaxM-bM-^HM-^R/M-bM-^HM-^R and NgfM-bM-^HM-^R/M-bM-^HM-^R; BaxM-bM-^HM-^R/M-bM-^HM-^R mice, DRGs were dissected and pooled from E14.5 NgfM-bM-^HM-^R/M-bM-^HM-^R; BaxM-bM-^HM-^R/M-bM-^HM-^R and BaxM-bM-^HM-^R/M-bM-^HM-^R embryos. Total RNA was extracted and directly subjected to microarray analysis. For the second screen comparing mouse DRG explants grown in the presence or absence of NGF, E13.5 mouse DRG explants were cultured for two days with 50 ng/ml of either NGF or NT3. Total RNA was extracted and then subjected to microarray analysis.
2013-11-01 | E-GEOD-25611 | biostudies-arrayexpress
Project description:We report that developmental competition between sympathetic neurons for survival is critically dependent on a sensitization process initiated by target innervation and mediated by a series of feedback loops. Target-derived nerve growth factor (NGF) promoted expression of its receptor TrkA in neurons and prolonged TrkA-mediated signals. NGF also controlled expression of brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), which, through the receptor p75, can kill neighboring neurons with low retrograde NGFâ??TrkA signaling whereas neurons with high NGFâ??TrkA signaling are protected. Perturbation of any of these feedback loops disrupts the dynamics of competition. We suggest that three target-initiated events are essential for rapid and robust competition between neurons: sensitization, paracrine apoptotic signaling, and protection from such effects. Experiment Overall Design: This experiment examine gene expression differences in superior cervical ganglia fro P0 bax null versus NGF-Bax double null animals. The Bax genotype was used in order to prevent the neuronal cell death normally observed in the NGF null animal.
2008-06-11 | E-GEOD-10498 | biostudies-arrayexpress
Project description:We report that developmental competition between sympathetic neurons for survival is critically dependent on a sensitization process initiated by target innervation and mediated by a series of feedback loops. Target-derived nerve growth factor (NGF) promoted expression of its receptor TrkA in neurons and prolonged TrkA-mediated signals. NGF also controlled expression of brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), which, through the receptor p75, can kill neighboring neurons with low retrograde NGF–TrkA signaling whereas neurons with high NGF–TrkA signaling are protected. Perturbation of any of these feedback loops disrupts the dynamics of competition. We suggest that three target-initiated events are essential for rapid and robust competition between neurons: sensitization, paracrine apoptotic signaling, and protection from such effects. Keywords: comparative gene expression analysis
2008-04-09 | GSE10498 | GEO
Project description:Peripheral afferent neurons terminate at the surfaces of tendons, yet their role after injury beyond nociceptive functions remain unclear. Using transgenic animal models, sensory neurons were found to sprout after Achilles tendon injury in domains of Nerve growth factor (NGF) expression. Conditional deletion of Ngf in either myeloid or mesenchymal cell types led to tendon repair defects – findings phenocopied by inactivation of TrkA (Tropomyosin receptor kinase A) using a knockin mouse model. We sought to identify the signals modulated with neural TrkA inhibition. A combination of single cell and spatial transcriptomic analysis was performed on the Achilles injury site of TrkA^F592A animals and compared them to TrkA^WT.
2023-11-27 | GSE245097 | GEO
Project description:Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment, not merely as a long-lasting cholinergic maintainer and neuroprotective agent but also as a direct anti-amyloidogenic factor. However, the development of a NGF-based therapy for neurodegenerative diseases is limited by the partial access of NGF to the brain and to its potent nociceptive actions in animals and humans. Indeed, NGF is involved in pain transmission and perception. The nociceptive activity of NGF is mediated through the activation of TrkA and p75NTR receptors on sensory nerve endings. Our group recently studied forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. This “painless” hNGF hNGFP61S/R100E displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo, via a selective alteration of TrkA versus p75NTR binding and signaling. The molecular mechanism through which pNGF reduces nociceptive activity has never been investigated, therefore we performed gene expression microarray analysis to investigated the effect of hNGF hNGFP61S/R100E delivery in rat Dorsal Root Ganglia.
2017-04-18 | GSE80257 | GEO
Project description:We used quantitative mass spectrometry-based proteomics to unravel global nerve growth factor (NGF)-induced TrkA signaling dynamics at the interactome, phosphoproteome and proteome level. A tetracycline-inducible system for TrkA expression was generated in the human neuroblastoma cell line, SH-SY5Y. TrkA-induced cells were stimulated with NGF for different time points to follow phosphoproteome, interactome and proteome changes on a temporal scale. In a triple SILAC setup (Light: Lys0,Arg0; Medium: Lys4,Arg6; and Heavy: Lys8,Arg10), the samples were stimulated with NGF as indicated. Phosphoproteome: 0, 10, 45 min and 0, 120, 120 min+cycloheximide. Interactome: 0, 5, 10 min. Proteome: 0, 24, 48 h. All experiments were performed as biological replicates.
2015-05-06 | PXD001115 | Pride
Project description:Background: Though exosomes, as the by-products of human umbilical cord mesenchymal stem cells (hUC-MSCs), have been demonstrated to be an effective therapy for traumatic spinal cord injury (SCI), it remains unclear through which manner exosomes act. Aim: In order to figure out whether exosomes attenuate lesion size of SCI by the amelioration of neuronal injury triggered by secondary inflammatory storm and induction of inner motivation of neurite outgrowth, we designed and performed this experiment. Methods: We determined absolute contents of all exosomal miRNAs and investigated the potential mechanisms of miR-199a-3p/145-5p in inducing neurite outgrowth in vivo and vitro. Results: miR-199a-3p/145-5p, which were relatively top-ranking miRNAs in exosomes, promoted PC12 cells differentiation suppressed by lipopolysaccharide (LPS) in vitro through the modulation of NGF/TrkA pathway. We also demonstrated that Cblb was the direct target of miR-199a-3p and Cbl was the direct target of miR-145-5p. Cblb and Cbl genes knock down revealed that TrkA ubiquitylation level significantly decreased, subsequently, activating the NGF/TrkA downstream pathways Akt and Erk. In return, overexpression of Cblb and Cbl suggested that TrkA ubiquitylation level significantly increased, subsequently, inactivating the NGF/TrkA downstream pathways Akt and Erk. Western blot and co-immunoprecipitation confirmed the direct interaction between TrkA and Cblb, TrkA and Cbl. In vivo experiment, exosomal miR-199a-3p/145-5p were found to up-regulate TrkA expression in the lesion site and promote locomotor function of SCI rats as well. Conclusion: In summary, our study suggested that hUC-MSCs derived exosomes may treat SCI by transferring miR-199a-3p/145-5p to neurons, and modulating TrkA ubiquitylation, and strengthening the NGF/TrkA signaling pathway in SCI rats.
2020-12-08 | GSE159814 | GEO
Project description:Peripheral afferent neurons terminate at the surfaces of tendons, yet their role after injury beyond nociceptive functions remain unclear. Using transgenic animal models, sensory neurons were found to sprout after Achilles tendon injury in domains of Nerve growth factor (NGF) expression. Conditional deletion of Ngf in either myeloid or mesenchymal cell types led to tendon repair defects – findings phenocopied by inactivation of TrkA (Tropomyosin receptor kinase A) using a knockin mouse model. We sought to identify the signals modulated with neural TrkA inhibition. A combination of single cell and spatial transcriptomic analysis was performed on the Achilles injury site of TrkAF592A animals and compared them to TrkAWT.
2023-11-27 | GSE244921 | GEO
Project description:Nerve growth factor (NGF) pays a role in neuronal differentiation and may also play a role in hematopoietic differentiation as shown by synergistic action for the colony formation of CD34 positive hematopoietic progenitor cells treated with M-CSF or SCF. However, the exact role of NGF in hematopoietic system is unclear. It is also not clear whether NGF mediated signals in hematopoietic cells are identical to those in neuronal cells. To study the signal transduction pathways induced by NGF treatment in hematopoietic cells, we utilized the mastocytoma cell line HMC-1 (V560G c-Kit) which expresses the NGF receptor, TrkA, as well as the constitutively activated SCF receptor, V560G c-Kit, which can be inhibited by treatment with tyrosine kinase inhibitor imatinib mesylate. NGF rescues HMC-1 (V560G c-Kit) from imatinib induced cell death and promotes proliferation. To examine the NGF mediated proliferation and survival in these cells, we compared the NGF mediated upregulated genes (30 and 120 min after stimulation) to the downregulated genes by imatinib treatment (downregulation of c-Kit activity for 4 h) by transcriptome analysis. The following conclusions can be drawn from the microarray data: Firstly, gene expression profiling reaveals 50% overlap of genes induced by NGF-TrkA with genes expressed downstream of V560G c-Kit. Secondly, NGF treatment does not enhance expression of genes involved in immune related functions that were down modulated by imatinib. Thirdly, more than 55% of common upregulated genes are involved in cell proliferation and survival. Forthly, we found KLF2 and SMAD7 as the NGF mediated novel down stream genes in hematopoietic cells that may play a role in NGF mediated survival signal in HMC-1 (V560G c-Kit) cells. Keywords: Transcriptome analysis - comparison of TrkA and V560G c-Kit downstream genes in HMC-1 (V560G c-Kit) cells In total, 4 samples were analyzed, one of which served as a common reference (HMC1 17h SerumStarv 4h Imatinib). This sample was labeled with Cy3. All additional samples were labeled with Cy5 and were cohybridized against the common reference. The first hybridization (M2370) represents a self-self-hybridization using the common reference.
2011-03-22 | E-GEOD-28045 | biostudies-arrayexpress
Project description:Nerve growth factor (NGF) pays a role in neuronal differentiation and may also play a role in hematopoietic differentiation as shown by synergistic action for the colony formation of CD34 positive hematopoietic progenitor cells treated with M-CSF or SCF. However, the exact role of NGF in hematopoietic system is unclear. It is also not clear whether NGF mediated signals in hematopoietic cells are identical to those in neuronal cells. To study the signal transduction pathways induced by NGF treatment in hematopoietic cells, we utilized the mastocytoma cell line HMC-1 (V560G c-Kit) which expresses the NGF receptor, TrkA, as well as the constitutively activated SCF receptor, V560G c-Kit, which can be inhibited by treatment with tyrosine kinase inhibitor imatinib mesylate. NGF rescues HMC-1 (V560G c-Kit) from imatinib induced cell death and promotes proliferation. To examine the NGF mediated proliferation and survival in these cells, we compared the NGF mediated upregulated genes (30 and 120 min after stimulation) to the downregulated genes by imatinib treatment (downregulation of c-Kit activity for 4 h) by transcriptome analysis. The following conclusions can be drawn from the microarray data: Firstly, gene expression profiling reaveals 50% overlap of genes induced by NGF-TrkA with genes expressed downstream of V560G c-Kit. Secondly, NGF treatment does not enhance expression of genes involved in immune related functions that were down modulated by imatinib. Thirdly, more than 55% of common upregulated genes are involved in cell proliferation and survival. Forthly, we found KLF2 and SMAD7 as the NGF mediated novel down stream genes in hematopoietic cells that may play a role in NGF mediated survival signal in HMC-1 (V560G c-Kit) cells. Keywords: Transcriptome analysis - comparison of TrkA and V560G c-Kit downstream genes in HMC-1 (V560G c-Kit) cells
2011-03-22 | GSE28045 | GEO