Differential contribution of P73+ Cajal-Retzius cells and Reelin to cortical morphogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE276037 | GEO | 2024/09/04
REPOSITORIES: GEO
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Project description:Precise spatiotemporal control of mRNA translation machinery is essential to proper development of highly complex systems like the neocortex. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stagedependent manner in mice. Neocortical absence of HuR alters the phosphorylation states of the initiation and elongation factors of the core translation machinery. In addition, HuR regulates the temporally specific positioning of functionally related mRNAs into the active translation sites, the polysomes. HuR also determines the specificity of neocortical polysomes by defining their combinatorial composition of ribosomal proteins and initiation and elongation factors. For some of the HuR-dependent proteins, the association with polysomes depends on the eIF2 alpha kinase 4 (eIF2ak4), which associated with HuR in prenatal developing neocortices. Finally, we found that deletion of HuR prior to embryonic day 10 (E10) disrupts both neocortical lamination and formation of the main neocortical commissure, the corpus callosum. Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity. Cortex was dissected from mouse pups at embryonic day 13 (E13) or the day of birth (P0).
2014-08-25 | E-GEOD-50809 | biostudies-arrayexpress
Project description:In this study, we determined the effect of chronic consistent hypoxia (CCH) and chronic intermittent hypoxia (CIH) on global gene expression in cortical and hippocampal region of developing mouse brain using long-oligo beadschip arrays. Keywords: Gene expression profile Control-Cortex: Cortical samples from 16 days old mice were analysed on whole-genome expression chips to reveal expression profile at this developmental stage. Used as control for Chronic Hypoxia Treated cortical samples. CCH-Cortex: Cortical samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression profile following 2-week CCH treatment. CIH-Cortex: Cortical samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression profile following 2-week CIH treatment. Control-Hippocampus: Hippocampal samples from 16 days old mice were analysed on whole-genome expression chips to reveal expression profile at this developmental stage. Used as control for Chronic Hypoxia Treated hippocampal samples. CCH-Hippocampus: Hippocampal samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression following 2-week CCH treatment. CIH-Hippocampus: Hippocampal samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression following 2-week CIH treatment.
2010-06-25 | E-GEOD-8262 | biostudies-arrayexpress
Project description:The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 ? Eomes ? Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism. To determine the role of Eomes in the propagation of the protomap to cortical plate neurons, used microarray analysis of E14.5 cortex from five wild type and three Eomes knockout mice.
2013-04-02 | E-GEOD-43387 | biostudies-arrayexpress
Project description:Objective: To elucidate the potential effects of stressful factors for depression on the hippocampal, frontal cortex and pituitary gland genome-wide transcriptomes at the molecular level, we evaluated the transcriptomic profiles of depression rats under chronic restraint stress (CRS). Methods: Forty-eight rats were randomly divided into control, model, fluoxetine and acupuncture groups. Experimental period was 28 days. Open-field test, Sucrose preference and body weight were investigated respectively at the experiment before and after the experiment. The experiment having been finished, solexa sequencing technology (Illumina Nextseq 500/151nt) was applied to investigate and verify the altered hippocampal, frontal cortex and pituitary gland genome-wide transcriptome analysis in rats of all groups. Results: Based on the data from RNA-seq analysis, it revealed that compared the expression of genes in the control group with model group in the respective of three brain tissues, 101, 134, 148 differential expression genes were found in the hippocampus, frontal cortex and pituitary gland, respectively; compared the expression of genes in the fluoxetine group with model group in the respective of three brain tissues, 41, 46, 87 differential expression genes were found in the hippocampus, frontal cortex and pituitary gland, respectively; compared the expression of genes in the acupuncture group with model group in the respective of three brain tissues, 107, 89, 179 differential expression genes were found in the hippocampus, frontal cortex and pituitary gland, respectively. Furthermore, we used the GO (Gene ontology) analysis and KEGG (Kyo-To conservation of Genes and Genomes) pathway analysis for these differentially expressed genes. We found that the results of these two analyses were consistent, both mainly related to monoamine neurotransmitters, inflammation and immune response in control group VS model group. It is noted that this phenomenon also appears in fluoxetine group compared with model group, acupuncture group VS model group. Importantly, the antidepressant effect of acupuncture was more extensive, which was more consistent with the pathogenesis of depression induced by CRS in rats. Conclusions: Our study represents the first detailed analysis of the hippocampal, frontal cortex and pituitary gland genome-wide transcriptomes in depression rats under CRS by RNA-seq technology. The results of this study revealed multiple DEGs and possible mechanisms specifying the function of hippocampal, frontal cortex and pituitary gland in depression rats induced by CRS. These results provide a basis for further investigation of the signaling mechanisms that affect central nervous system output related to stress-sensitive depressive disorder development.
2017-09-24 | GSE86392 | GEO
Project description:The human brain's temporal lobe contains the entorhinal cortex (EC), a highly interconnected integrative hub for sensory and spatial information; key for episodic memory formation and the primary source of cortical hippocampal inputs. The human EC continues to develop during childhood, yet neurogenesis and neuronal migration to the EC are widely considered complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions; with a large tangential stream persisting ~1 year and radial dispersal until ~2-3 years. In contrast, we found no equivalent postnatal migration in rhesus macaque (Macaca mulatta). Immunostaining and single-nuclei RNA-seq (snRNA-seq) of ganglionic eminence (GE) germinal zones, EC stream, and postnatal EC reveals that most EC stream migrating cells are derived from the caudal GE and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life when children are actively interacting with their environment. The EC is one of the first brain regions affected in Alzheimer’s disease and recent work links the decline in cognitive function to the loss of LAMP5+RELN+ cells. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.
2023-09-26 | GSE199762 | GEO
Project description:Oriented cell divisions are critical for the formation and maintenance of structured epithelia. Proper mitotic spindle orientation relies on polarised anchoring of force generators to the cell cortex by the evolutionarily conserved Gαi-LGN-NuMA complex. However, the polarity cues that control cortical patterning of this ternary complex remain largely unknown in mammalian epithelia. Here we identify the membrane-associated protein Annexin A1 (ANXA1) as a novel interactor of LGN in mammary epithelial cells. ANXA1 acts independently of Gαi to instruct the accumulation of LGN and NuMA at the lateral cortex to ensure cortical anchoring of Dynein-Dynactin and astral microtubules and thereby planar alignment of the mitotic spindle. Loss of ANXA1 randomises mitotic spindle orientation, which in turn disrupts epithelial architecture and lumen formation in three-dimensional (3D) primary mammary organoids. Our findings establish ANXA1 as an upstream cortical cue that regulates LGN to direct planar cell divisions during mammalian epithelial morphogenesis.
2022-12-02 | PXD027452 | Pride
Project description:<h4><strong>INTRODUCTION: </strong>Approximately 1% of the world's population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet, a high-fat, low-carbohydrate diet. Despite the KD's success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation.</h4><h4><strong>OBJECTIVES: </strong>The goal of this study was to explore changes in the lipidome in hippocampal and cortical tissue from Kv1.1-KO model of epilepsy.</h4><h4><strong>METHODS: </strong>FT-ICR/MS analysis was utilized to examine nonpolar metabolome of cortical and hippocampal tissue isolated from a Kv1.1 channel knockout mouse model of epilepsy (n = 5) and wild-type mice (n = 5).</h4><h4><strong>RESULTS: </strong>Distinct metabolic profiles were observed, significant (p < 0.05) features in hippocampus often being upregulated (FC ≥ 2) and the cortex being downregulated (FC ≤ 0.5). Pathway enrichment analysis shows lipid biosynthesis was affected. Partition ratio analysis revealed that the ratio of most metabolites tended to be increased in Kv1.1-/-. Metabolites in hippocampal tissue were commonly upregulated, suggesting seizure initiation in the hippocampus. Aberrant mitochondrial function is implicated by the upregulation of cardiolipin, a common component in the mitochondrial membrane.</h4><h4><strong>CONCLUSION: </strong>Generally, our study finds that the lipidome is changed in the hippocampus and cortex in response to Kv1.1-KO indicating changes in membrane structural integrity and synaptic transmission.</h4>
2022-01-06 | MTBLS1432 | MetaboLights
Project description:Neuroserpin is a serine protease inhibitor that regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin is strongly expressed during nervous system development as well as during adulthood, when it is predominantly found in regions eliciting synaptic plasticity. In the hippocampus, neuroserpin regulates developmental neurogenesis, synaptic maturation and in adult mice it modulates synaptic plasticity and controls cognitive and social behavior. High expression levels of neuroserpin in the cerebral cortex starting from prenatal stage and persisting during adulthood suggest an important role for the serpin in the formation of this brain region and in the maintenance of cortical functions. In order to uncover neuroserpin function in the cerebral cortex, in this work we performed a comprehensive investigation of its expression pattern during development and in the adulthood. Moreover, we assessed the role of neuroserpin in cortex formation by comparing cortical lamination and neuronal maturation between neuroserpin-deficient and control mice. Finally, we evaluated a possible regulatory role of neuroserpin at cortical synapses in neuroserpin-deficient mice. We observed that neuroserpin is expressed starting from the beginning of corticogenesis until adulthood throughout the cortex in both glutamatergic projection neurons and GABA-ergic interneurons. However, in the absence of neuroserpin we did not detect any alteration in cortical layer formation, in soma size, in dendritic length, and the ultrastructure. Furthermore no significant quantitative changes could be observed in the proteome of cortical synapses could be observed upon Neuroserpin deficiency. We conclude that, although strongly expressed in the cerebral cortex, absence of neuroserpin does not lead to developmental abnormalities, and does not perturb composition of the cortical synaptic proteome.
2021-02-23 | PXD022371 | Pride
Project description:Neocortical circuits consist of stereotypical motifs that must self-assemble during development. Recent evidence suggests the subtype identity of both excitatory projection neurons (PNs) and inhibitory interneurons (INs) is important for this process. We knocked out the transcription factor Satb2 in PNs to induce those of the intratelencephalic (IT)-type to adopt a pyramidal tract (PT)-type identity. Loss of IT-type PNs selectively disrupted the lamination and circuit integration of INs derived from the caudal ganglionic eminence (CGE). Strikingly, reprogrammed PNs demonstrated reduced synaptic targeting of CGE-derived INs relative to controls. In control mice, IT-type PNs targeted neighboring CGE INs while PT-type PNs did not in deep layers, confirming this lineage-dependent motif. Finally, single cell RNA-sequencing revealed that major CGE IN subtypes were conserved after loss of IT PNs, but with differential transcription of synaptic proteins and signaling molecules. Thus, IT-type PNs influence CGE-derived INs in a non-cell autonomous manner during cortical development.
2019-03-06 | GSE127724 | GEO
Project description:Purpose:This work aimed to identify the genetic profiles of piriform projection neurons and characterize their spatial organization within the piriform cortex. Methods: We microdissected the three layers of pirifrom cortex by laser capture (LMD) and performed RNA deep sequencing in order to identify layer-specific molecular markers, we then validated these data by using RNA in situ hybridization and immunohistochemistry.We next performed anterograde neural tracing experiments to identify piriform target regions, and retrograde neural tracing experiments to analyze how piriform projection neurons are organized within piriform cortex.We then combined the analysis of patterns of gene expression with retrograde tracing experiments to identify molecular signatures of the different subclasses of piriform projecting neurons. Results:We show that layers and sub-layers of the piriform cortex can be discriminated by gene expression patterns in adult piriform cortex. We observe that neurons projecting to distinct target areas are localized in distinct layers and express specific genes. We demonstrate that these molecular signatures of piriform projection neurons are maintained in reeler mice, in which cortical lamination is lost and neural positioning is scrambled, suggesting that piriform output connectivity strictly depends on the molecular programm, rather than a proper lamination of the cortex. Conclusion:These results provide important insights into the principles underling the piriform connectivity.
2016-07-13 | GSE70800 | GEO