Heteromeric Kv1.2 channels counteract persistent sodium currents in proprioceptive DRG neurons
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PROVIDER: PRJNA1170245 | ENA |
REPOSITORIES: ENA
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Project description:During development neurons achieve a high degree of specialization (Fishell and Heintz, 2013). Over time, while continuously recycling their components and despite transcriptional noise, their own respective properties remain intact. The transcription factors that play a large role in initially establishing neuronal identity can be required for maintaining it (Deneris and Hobert, 2014). Post-transcriptional regulation is also important to differentiation (Bian and Sun, 2011) but its role in maintaining cell identity is less established. To better understand how post-transcriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory class, whose properties are well established and display clear differences when compared to other neurons in the ganglion. By conditionally ablating Dicer in mice, using a parvalbumin (Pvalb) driven cre, we impaired post-transcriptional regulation in the proprioceptive sensory neuron population. KO animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is mirrored by a cell-death within the DRG. Before cell-loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of non-proprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Post-transcriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons.
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Project description:The goal of this study was to analyze global gene expression in specific populations of somatosensory neurons in the periphery, including major, non-overlapping populations that include nociceptors, pruriceptors, and prorioceptors. The mammalian somatosensory nervous system encodes the perception of specific environmental stimuli. The dorsal root ganglion (DRG) contains distinct somatosensory neuron subtypes that innervate diverse peripheral tissues, mediating the detection of thermal, mechanical, proprioceptive, pruriceptive, and nociceptive stimuli. We purified discrete subtypes of mouse DRG somatosensory neurons by flow cytometry using fluorescently labeled mouse lines (SNS-Cre/TdTomato, Parv-Cre/TdTomato) in combination with Isolectin B4-FITC surface staining (IB4). This allowed identification of transcriptional differences between these major populations, revealing enrichment of voltage-gated ion channels, TRP channels, G-protein coupled receptors, transcription factors, and other functionally important classes of genes within specific somatosensory neuron subsets.
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Project description:The goal of this study was to analyze global gene expression in specific populations of somatosensory neurons in the periphery, including major, non-overlapping populations that include nociceptors, pruriceptors, and prorioceptors. The mammalian somatosensory nervous system encodes the perception of specific environmental stimuli. The dorsal root ganglion (DRG) contains distinct somatosensory neuron subtypes that innervate diverse peripheral tissues, mediating the detection of thermal, mechanical, proprioceptive, pruriceptive, and nociceptive stimuli. We purified discrete subtypes of mouse DRG somatosensory neurons by flow cytometry using fluorescently labeled mouse lines (SNS-Cre/TdTomato, Parv-Cre/TdTomato) in combination with Isolectin B4-FITC surface staining (IB4). This allowed identification of transcriptional differences between these major populations, revealing enrichment of voltage-gated ion channels, TRP channels, G-protein coupled receptors, transcription factors, and other functionally important classes of genes within specific somatosensory neuron subsets. SNS-Cre mice were bred with Rosa26-TdTomato mice to generate SNS-Cre/TdTomato reporter mice. Parv-Cre mice were bred with Rosa26-TdTomato mice to generate Parv-Cre/TdTomato mice. Isolectin B4-FITC was used to stain the surface of SNS-Cre/TdTomato reporter mice. We used these strategies of fluorescent labeling to purify distinct murine sensory neuron subsets from the dorsal root ganglia (DRG) by fluorescence activated cell sorting (FACS). Neurons were sorted directly in Qiazol for total RNA extraction and microarray analysis. Whole DRG tissue was also included for transcriptome analysis to compare with purified neuronal populations.
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Project description:Proprioception relies on two main classes of proprioceptive sensory neurons (pSNs). These neurons innervate two distinct peripheral receptors in muscle, muscle spindles (MSs) or Golgi tendon organs (GTOs), and synapse onto different sets of spinal targets, but the molecular basis of their distinct pSN subtype identity remains unknown. We used microarray analysis to compare gene expression profiles between MS- and GTO- innervating proprioceptors.
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