Identification of the genes under the control of the transcription factor Prdm12 in somatosensory neurons
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE118187 | GEO | 2019/04/05
REPOSITORIES: GEO
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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.
2013-11-01 | GSE25611 | 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: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:Primary somatosensory neurons are diverse neurons that report salient features of our internal and external environments. How specialized gene expression programs emerge during development to endow each somatosensory neuron subtype with unique properties is unclear. To analyze the developmental progression of transcriptional maturation of each principal somatosensory neuron subtype, we generated a transcriptomic atlas of cells traversing the somatosensory lineage. We find that somatosensory neurogenesis leads to neurons in a transcriptionally unspecialized state, characterized by trace expression of subtype-specific genes yet co-expression of transcription factors (TFs) that become restricted to select subtypes as development proceeds. Single cell transcriptomic analysis using sensory neurons from mutant mice lacking representative broad-to-restricted TFs revealed that they are essential for establishing subtype specific gene programs in subtypes where their expression is maintained, while leaving other subtypes unaffected. We also identify a role for neuronal targets by demonstrating that nerve growth factor influences subtype-restricted patterns of TFs. Our findings support a model in which extrinsic cues orchestrate somatosensory neuron diversification by influencing the expression pattern of TFs that promote transcriptional specialization of somatosensory neuron subtypes.
2019-10-19 | GSE139088 | GEO
Project description:V1 interneurons are a class of inhibitory neurons that play an essential role in vertebrate locomotion; however, the factors contributing to their specification are poorly understood. Morphological and molecular evidence suggest that the zinc finger transcription factor Prdm12 may play a role in promoting V1 interneurons while repressing V2 and V0 fates. Here, we performed RNAseq on Xenopus laevis ectoderm converted to posteriorized neural tissue (with noggin and retinoic acid) in the presence or absence of a series of Prdm12 constructs (wild-type Prdm12, Prdm12-VP16, and Prdm12-engrailed-repressor). We also performed ChIPseq on a Prdm12-FLAG in wild-type or posteriorized neuralized (with noggin and retinoic acid) X. laevis ectoderm. Taken together, these data demonstrate Prdm12's genomic targets and their downstream transcription. X. laevis embryos were injected with mRNAs encoding prdm12 constructs, along with the bmp inhibitor noggin. Presumptive ectoderm (neuralized by noggin) was dissected and treated with retinoic acid. Samples were then processed into RNAseq libraries or prdm12-FLAG was immunoprecipitated and its targets sequenced. Background was input prior to IP.
2015-11-04 | E-GEOD-64551 | biostudies-arrayexpress
Project description:Prdm12 is a key transcription factor in nociceptor neurogenesis. Mutations of Prdm12 cause Congenital Insensitivity to Pain (CIP) due to failure of nociceptor development. However, precisely how deletion of Prdm12 during development or adulthood affects nociception is unknown. Here, we employ tissue- and temporal-specific knockout mouse models to test the function of Prdm12 during development and in adulthood. We find that constitutive loss of Prdm12 causes deficiencies in proliferation during sensory neurogenesis. We also demonstrate that conditional knockout from dorsal root ganglia (DRGs) during embryogenesis causes defects in nociception. In contrast, we find that in adult DRGs, Prdm12 is dispensable for most pain sensation and injury-induced hypersensitivity. Using transcriptomic analysis, we found mostly unique changes in adult Prdm12 knockout DRGs compared to embryonic knockout, and that PRDM12 is likely a transcriptional activator in the adult. Overall, we find that the function of PRDM12 changes over developmental time.
2021-02-25 | GSE167468 | 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:Although DNA methylation plays a critical role in the development and function of mammalian central nervous system (CNS), its role in peripheral neurons has not been elucidated. To address this issue, we produced conditional knockout mice (CKO) specifically deleting the gene for maintenance DNA methyltransferase 1 (Dnmt1) during the development of neural crest cells. Despite global hypomethylation in the embryonic dorsal root ganglion (DRG) of the CKO mice, the number of sensory neurons was relatively unaffected. However, expression of many genes required for sensory neuron development was altered in embryonic mutant DRG, including down-regulation of Runx1 and TrkA genes as well as up-regulation of Id1 and Dtx1, two negative regulators for neurogenesis. Accompanied with the downregulation of an NGF receptor TrkA, the peripheral axonal projection and the branching of sensory neurons were impaired. Furthermore, the expression of the neuropeptide Galanin and several vanilloid receptors such as TrpV1 and TrpM8 were not detected in the DRG of the CKO mice during late embryonic and neonatal stages, suggesting that DNA methylation regulates the differentiation program for a subset of nociceptive sensory neurons. Taken together, our findings suggest that through transcriptional regulation of key developmental genes in sensory neurons, DNA methylation play a key role in the control of the axonal projection and fate specification of peripheral sensory neurons. We compared gene expression patterns in Wildtype and DNA methylation deficient (Wnt1-cre; Dnmt1 mutant) mouse dorsal cortex. We performed 4 replicates using different each individual mouse strain. The Sample GSM565172 table is the average log ratio for the 4 replicatesArrays were performed.
2011-12-01 | E-GEOD-23530 | biostudies-arrayexpress
Project description:Nociceptive neurons develop a complex dendritic arbor to sense noxious stimuli, which enables animals to react to environmental insults and perform self-protective behaviours. The genetic programs controlling neuronal dendritic morphogenesis are poorly understood. In C. elegans, the PVD sensory neuron generates a complex dendritic arbor that envelops the body of the animal. This nociceptive neuron enables study of dendrite formation in vivo. We used expression arrays to identify genes highly enriched in the PVD neuron while undergoing dendritic morphogenesis. These genes could function in pathways controlling dendrite formation.
2010-06-16 | GSE21162 | GEO
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