Single Cell sequencing of E14.5, E15.5 and E14.5 Kir electroporated cortical neurons.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE115628 | GEO | 2018/06/12
REPOSITORIES: GEO
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Project description:Experimental in vivo hyperpolarization of E14.5 apical progenitors shifted their transcriptional programs with precocious generation of intermediate progenitors, and a forward shift in the laminar, molecular, morphological and circuit features of their neuronal progeny. In particular, we reported an overall repression of L4-type neuronal genes and a premature induction of L2/3-type neuronal genes following Kir2.1 overexpression.
2018-06-12 | GSE115627 | GEO
Project description:Single Cell sequencing of E14.5, E15.5 and E14.5 Kir electroporated cortical neurons.
| PRJNA475585 | ENA
Project description:To assess the requirement of Nova2 for alternative processing of RNA in the developping brain. Neuronal migration leads to a highly organized laminar structure in the mammalian brain and its mis-regulation causes lissencephaly, behavioral and cognitive defects. Reelin signaling, mediated in part by a key adaptor, disabled-1 (Dab1), plays a critical but incompletely understood role in this process. We found that the neuron-specific RNA binding protein Nova2 regulates neuronal migration in late-generated cortical and Purkinje neurons. An unbiased HITS-CLIP and exon junction array search for Nova-dependent RNAs at E14.5 focused on components of the reelin pathway revealed only one candidate—an alternatively spliced isoform of Dab1 (Dab1.7bc). In utero electroporation demonstrated that Dab1.7bc was sufficient to induce neuronal migration defects in wild-type mice and exacerbate defects when Dab1 levels were reduced, while Dab1 overexpression mitigates defects in Nova2-null mice. Thus Nova2 regulates an RNA switch controlling the ability of Dab1 to mediate neuronal responsiveness to reelin signaling and neuronal migration, suggesting new links between splicing regulation, brain disease and development. Keywords: Comparative analysis RNA from the cortex of 3 wild type and 3 Nova2 KO E14.5 cortex. One array per biological replicate.
2010-07-07 | E-GEOD-22758 | biostudies-arrayexpress
Project description:To assess the requirement of Nova2 for alternative processing of RNA in the developping brain. Neuronal migration leads to a highly organized laminar structure in the mammalian brain and its mis-regulation causes lissencephaly, behavioral and cognitive defects. Reelin signaling, mediated in part by a key adaptor, disabled-1 (Dab1), plays a critical but incompletely understood role in this process. We found that the neuron-specific RNA binding protein Nova2 regulates neuronal migration in late-generated cortical and Purkinje neurons. An unbiased HITS-CLIP and exon junction array search for Nova-dependent RNAs at E14.5 focused on components of the reelin pathway revealed only one candidate—an alternatively spliced isoform of Dab1 (Dab1.7bc). In utero electroporation demonstrated that Dab1.7bc was sufficient to induce neuronal migration defects in wild-type mice and exacerbate defects when Dab1 levels were reduced, while Dab1 overexpression mitigates defects in Nova2-null mice. Thus Nova2 regulates an RNA switch controlling the ability of Dab1 to mediate neuronal responsiveness to reelin signaling and neuronal migration, suggesting new links between splicing regulation, brain disease and development. Keywords: Comparative analysis
2010-07-07 | GSE22758 | GEO
Project description:Kir2.1 has been implicated in a number of channelopathies including Andersen-Tawil Syndrome, Short QT Syndrome and catecholaminergic polymorphic ventricular tachycardia. We developed a mass spectrometry-based assay to identify phosphorylation sites and test the functional consequence of removing those sites by site-directed mutagenesis. Our study identified novel sites of phosphorylation and suggests that the site of phosphorylation can influence channel function. We envision our approach can be readily adapted to study additional mutations and other ion channels.
2021-11-03 | PXD024662 | Pride
Project description:We profiled the transcriptomic changes that occur in the Drosophila third antennal segment after silencing the second order olfactory neurons in the antennal lobe with Kir2.1 (EH1). A non-conducting variant of Kir2.1 (Kir2.1-nc or EH2) served as our control.
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Project description:TRIM9 and TRIM67 are neuronally-enriched E3 ubiquitin ligases essential for neuronal morphogenesis and responses to the axon guidance cue netrin-1. Deletion of either gene in the mouse results in subtle neuroanatomical anomalies yet overt deficits in spatial learning and memory. The identify of few TRIM9 or TRIM67 substrates are known. Here we performed ubiquitin remnant profiling approach (Xu et al., 2010)in cultured cortical neurons from murine wildtype, Trim9-/-, Trim67-/-, and Trim9-/-:Trim67-/- embryos cultured with or without netrin-1 supplementation to attempt to identify proteins with altered ubiquitination. Although batch variability hindered our ability to identify differential protein ubiquitination, the results delineate the neuronal ubiquitionome during neurite outgrowth, axon specification, and axon branching.
2021-01-04 | PXD021818 | Pride
Project description:Kir2.1, an inward rectifier potassium channel, plays an important role in controlling membrane potential specially in cardiomyocytes. Here we explore its interactome via proximity biotin labeling and affinity purification approach (BioID). First, BioID membrane controls were generated with randomly selected transmembrane domains from yeast proteins, demonstrating the identification of membrane-associated proteins more than GFP or NLS controls. Using this control and a mutation from Andersen-Tawil syndrome which causes Kir2.1 Golgi accumulation, we have identified the most comprehensive Kir2.1 interactome and also found clues to its spatial information in subcellular levels. The interactome is showing that Kir2.1 in plasma membrane is surrounded by desmosome, integrin, cadherin and dystrophin-glycoprotein complex complexes, and supported by MAGUK family scaffold proteins. On the other hand, Kir2.1 mutant BioID revealed the COPII-mediated delivery of Kir2.1 from ER to Golgi and lysosome-mediated degradation of Golgi-accumulated and/or retrograde Kir2.1. Validating the interactome with co-immunoprecipitation, confocal microscope, and patch clamp analysis, we concluded that Kir2.1 is located in the defined membrane environment and is actively regulated by endosomal sorting for lysosome degradation.
2020-06-17 | PXD011004 | Pride
Project description:The integration of adult-born neurons in the existent neural circuitry is known to be activity-dependent. To decipher the underlying mechanisms, we genetically manipulated excitability of adult-born cells (via cell-specific overexpression of either Kv1.2 or Kir2.1 K+ channels). Longitudinal in vivo Ca2+ imaging and transcriptome analyses revealed that endogenous but not sensory-driven activity governs migration, morphogenesis, survival, and functional integration of adult-born juxtaglomerular neurons in the mouse olfactory bulb. The proper development of these cells required fluctuations of cytosolic Ca2+ levels, phosphorylation of CREB, and pCREB-mediated gene expression. Attenuating Ca2+ fluctuations via K+ channel overexpression strongly downregulated genes involved in neuronal migration, differentiation, and morphogenesis and upregulated the apoptosis-related genes, thus locking adult-born cells in the vulnerable and immature state. Together, the data identify signaling pathways connecting the endogenous intermittent neuronal activity/Ca2+ fluctuations as well as proper Kv1.2/Kir2.1 K+ channel function to migration, maturation, and survival of adult-born neurons.
2021-04-01 | GSE168349 | GEO
Project description:Neocortical excitatory neurons belong to diverse cell types, which can be distinguished by their dates of birth, laminar location, connectivity and molecular identities. During embryogenesis, apical progenitors (APs) located in the ventricular zone first give birth to deep-layer neurons, and next to superficial-layer neurons. While the overall sequential construction of neocortical layers is well-established, whether multiple neuron types are produced by APs at single time points of corticogenesis is unknown. To address this question, here we used FlashTag to fate-map simultaneously-born (i.e. isochronic) cohorts of AP-born neurons at successive stages of corticogenesis. We reveal that early in corticogenesis, isochronic neurons differentiate into heterogeneous laminar, hodological and molecular cell types. Later on, instead, simultaneously-born neurons have more homogeneous fates. Using single-cell gene expression analyses, we identify an early postmitotic surge in the molecular heterogeneity of nascent neurons during which some early-born neurons initiate and partially execute late-born neuron transcriptional programs. Together, these findings suggest that as corticogenesis unfolds, mechanisms allowing increased homogeneity in neuronal output are progressively implemented, resulting in progressively more predictable neuronal identities.
2022-04-20 | GSE191205 | GEO