Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA157839 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The assembly of neural circuits involves multiple sequential steps such as the specification of cell types, their migration to proper brain locations, morphological and physiological differentiation, and the formation and maturation of synaptic connections. This intricate and often prolonged process is guided by elaborate genetic mechanisms that regulate each developmental event. Evidence from numerous systems suggests that each cell type, once specified, is endowed with a genetic program that directs its subsequent development. This cell intrinsic program unfolds in respond to, and is regulated by, extrinsic signals, including cell-cell and synaptic interactions. To a large extent, the execution of this genetic program is achieved by the expression of specific sets of genes that support distinct developmental processes. Therefore, a comprehensive analysis of the developmental progression of gene expression in synaptic partners of neurons may provide a basis for exploring the genetic mechanisms regulating circuit assembly. Here we examined the developmental gene expression profiles in well defined cell types in a stereotyped microcircuit of the cerebellar cortex. Manually sorted pure populations of Purkinje cells and Stellate/Basket cells, 3 biological replicates, from Gad67-GFP bac-transgenic (G42) mice were profiled during postnatal developmental stages P3, P7, P14, P21, P28, P35 and P56 using Affymetrix MOE430.2 expression array
2012-07-19 | E-GEOD-37055 | biostudies-arrayexpress
Project description:We analyzed Purkinje cell transcriptome dynamics in the developing mouse cerebellum during the first three postnatal weeks, a key developmental period equivalent to the third trimester in human cerebellar development. Our study represents the first detailed analysis of developmental Purkinje cell transcriptomes and provides a valuable dataset for gene network analyses and biological questions on genes implicated in cerebellar and Purkinje cell development.
2019-01-31 | GSE86824 | GEO
Project description:The axon initial segment (AIS) is essential for initiating action potentials and maintaining neuronal polarity, yet the developmental roles of its core molecular components—Neurofascin 186 (NF186) and Ankyrin G (AnkG)—remain incompletely defined in cerebellar Purkinje cells. Here, we generated Purkinje cell-specific NF186/AnkG double knockout mice to investigate how these adhesion and scaffolding proteins cooperatively regulate AIS formation, ion channel localization, synaptic targeting, and neuronal survival. We found that combined deletion of NF186 and AnkG markedly disrupted assembly and maintenance of the AIS cytoskeleton during postnatal development. Other AIS-enriched proteins, including βIV Spectrin (βIVSpec), voltage-gated sodium (Nav) and potassium (Kv1.2) channels, failed to properly localize to the AIS and progressively disintegrated between postnatal days 10 and 30. Notably, Kv1.2 clustering in the pinceau synapse was disrupted, and basket cell axons showed misaligned terminal organization, indicating defective inhibitory synapse innervation. By two months of age, degeneration of Purkinje cells was evident, accompanied by cerebellar dysfunction. In addition, our RNA-seq analysis revealed that Purkinje cell-specific loss of NF186 predominantly activated immune-inflammatory pathways, AnkG loss significantly disrupted neuronal developmental and metabolic processes, and the dual loss of NF186/AnkG produced transcriptional changes that were distinct from, and in part intermediate to, those observed in every single knockout. Collectively, our results show that NF186 and AnkG have complementary, non-redundant roles to establish and maintain the Purkinje cell AIS, and that their loss disrupts synaptic organization at the AIS. These findings advance our understanding of AIS development in cerebellar neurons and have implications for diseases involving AIS dysfunction, including cerebellar ataxia and demyelinating neuropathies.
2026-03-27 | GSE322737 | GEO
Project description:During the first 10 postnatal days of mouse development, Purkinje cells, neurons of the cerebellum, pass through different developmental processes of differentiation such as profound dendritic remodeling and growth, cell death and loss of their ability to regenerate their axons. To identify the genes involved in these different processes and in particular transcription factors, the gene expression patterns of murine cerebellar cortical area centered on Purkinje soma have been measured using Affymetrix microarrays at 5 different developmental stages (postnatal days P0, P3, P5, P7 and P10; 4 replicates = 4 independent measurements for each stage).
2012-03-15 | E-MEXP-3444 | biostudies-arrayexpress
Project description:The emergence of functional cerebellar circuits is heavily influenced by activity-dependent processes. However, the contribution of intrinsic Purkinje cell activity to cerebellar development remains less understood. Here, we demonstrate that before synaptic networks mature, Purkinje cell intrinsic activity is essential for regulating dendritic growth, establishing connections with cerebellar nuclei, and ensuring proper cerebellar function. Disrupting this activity during the postnatal period impairs motor function, with earlier perturbations causing more severe deficits. Importantly, only early developmental disruptions lead to pronounced defects in cellular morphology, highlighting key temporal windows for dendritic growth and maturation. Transcriptomic analyses reveal that early intrinsic activity drives the expression of activity-dependent genes, including Prkcg and Car8, which are essential for dendritic development. Our findings emphasize the importance of temporally regulated intrinsic activity in Purkinje cells in guiding cerebellar circuit development, providing a potential unifying mechanism underlying cerebellum-associated disorders.
2026-02-03 | GSE294208 | GEO
Project description:The signalling protein PKCγ is a major regulator of Purkinje cell development and synaptic function. We have shown previously that increased PKCγ activity impairs dendritic development of cerebellar Purkinje cells. Mutations in the protein kinase Cγ gene (PRKCG) cause spinocerebellar ataxia type 14 (SCA14). In a transgenic mouse model of SCA14 expressing the human S361G mutation, Purkinje cell dendritic development is impaired in cerebellar slice cultures similar to pharmacological activation of PKC. The mechanisms of PKCγ-driven inhibition of dendritic growth are still unclear. Using immunoprecipitation-coupled mass spectrometry analysis we have identified Collapsin Response Mediator Protein 2 (CRMP2) as a protein interacting with constitutive active PKCγ(S361G) and confirmed the interaction with the Duolink™ proximity ligation assay. We show that in cerebellar slice cultures from PKCγ(S361G)- mice, phosphorylation of CRMP2 at the known PKC target site Thr555 is increased in Purkinje cells confirming phosphorylation of CRMP2 by PKCγ. miRNA-mediated CRMP2 knockdown decreased Purkinje cell dendritic outgrowth in dissociated cerebellar cultures as did the transfection of CRMP2 mutants with a modified Thr555 site. In contrast, dendritic development was normal after wildtype CRMP2 overexpression. In a novel knock-in mouse expressing only the phospho-defective T555A-mutant CRMP2, Purkinje cell dendritic development was reduced in dissociated cultures. This reduction could be rescued by transfecting wildtype CRMP2 but only partially by the phospho-mimetic T555D-mutant. Our findings establish CRMP2 as an important target of PKCγ phosphorylation in Purkinje cells mediating its control of dendritic development. Dynamic regulation of CRMP2 phosphorylation via PKCγ is required for its correct function.
2022-02-24 | PXD020124 | Pride
Project description:To model human cerebellar disease, we developed a novel, reproducible method to generate cerebellar Purkinje cells (PCs) from human pluripotent stem cells (hPSCs) that formed synapses when cultured with mouse granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. Using translating ribosomal affinity purification (TRAP) to compare gene expression of differentiating hPSC-PCs to developing mouse PCs, we found hPSC-PCs to be most similar to late juvenile (P21) mouse PCs. Analysis of mouse PCs defined novel developmental expression patterns for mitochondria and autophagy associated genes, recapitulated in hPSC-PCs. We further identified species differences in gene expression and confirmed protein expression of CD40LG in native human, but not mouse PCs. This study provides a robust method for generating relatively mature hPSC-PCs with human specific gene expression and defines novel genetic features in comparison to the first comprehensive analysis of global gene expression patterns of postnatal mouse PC development.
2020-06-18 | GSE140306 | GEO
Project description:To model human cerebellar disease, we developed a novel, reproducible method to generate cerebellar Purkinje cells (PCs) from human pluripotent stem cells (hPSCs) that formed synapses when cultured with mouse granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. Using translating ribosomal affinity purification (TRAP) to compare gene expression of differentiating hPSC-PCs to developing mouse PCs, we found hPSC-PCs to be most similar to late juvenile (P21) mouse PCs. Analysis of mouse PCs defined novel developmental expression patterns for mitochondria and autophagy associated genes, recapitulated in hPSC-PCs. We further identified species differences in gene expression and confirmed protein expression of CD40LG in native human, but not mouse PCs. This study provides a robust method for generating relatively mature hPSC-PCs with human specific gene expression and defines novel genetic features in comparison to the first comprehensive analysis of global gene expression patterns of postnatal mouse PC development.
2020-06-18 | GSE140301 | GEO
Project description:To model human cerebellar disease, we developed a novel, reproducible method to generate cerebellar Purkinje cells (PCs) from human pluripotent stem cells (hPSCs) that formed synapses when cultured with mouse granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. Using translating ribosomal affinity purification (TRAP) to compare gene expression of differentiating hPSC-PCs to developing mouse PCs, we found hPSC-PCs to be most similar to late juvenile (P21) mouse PCs. Analysis of mouse PCs defined novel developmental expression patterns for mitochondria and autophagy associated genes, recapitulated in hPSC-PCs. We further identified species differences in gene expression and confirmed protein expression of CD40LG in native human, but not mouse PCs. This study provides a robust method for generating relatively mature hPSC-PCs with human specific gene expression and defines novel genetic features in comparison to the first comprehensive analysis of global gene expression patterns of postnatal mouse PC development.
2020-06-18 | GSE140299 | GEO
Project description:We performed gene-expression analysis of mouse cerebellar granule cell layer as compared to that of Purkinje cells. DNA microarray analysis detected genes in cerebellar granule cell layer, most of which are classified into functional molecule categories. Our comparative analysis between Purkinje cells and the granule cell layer showed that the characteristic expression pattern in Purkinje cells was particularly represented by M-bM-^@M-^\the neural communication systemM-bM-^@M-^] components. Pukinje cells and granule cell layer of the mouse cerebellum were collected by laser microdissection for RNA extraction and hybridization on Affymetrix microarrays.
2013-01-17 | E-GEOD-26750 | biostudies-arrayexpress