Pax6 mutant neocortex vs. wild type
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE32271 | GEO | 2011/10/31
SECONDARY ACCESSION(S): PRJNA147319
REPOSITORIES: GEO
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Project description:Pax6 is a transcription factor with key functional roles in embryonic development. In order to identify downstream effectors of Pax6 in the developing cerebral cortex we performed microarray analysis. We compared gene expression profiles of cortical tissues isolated from wild type and Pax6-/- mouse embryos. In order to identify Pax6 downstream targets we carried out microarray analysis of Pax6-/- mutant mice. Pax6 is highly expressed in the mouse cerebral cortex at embryonic day E14.5, therefore we selected this tissue in order to compare gene expression profiles between wild type and Pax6-/- homozygous cortici. RNA samples were isolated from three mutant and three wild type embryos.
2011-10-31 | E-GEOD-32271 | biostudies-arrayexpress
Project description:The mechanisms by which the early spatiotemporal expression patterns of transcription factors such as Pax6 regulate the region-specific proliferation rates of neural progenitors are poorly understood. Pax6 is expressed in a gradient across the developing cortex and is essential for normal corticogenesis. We found that constitutive or conditional loss of Pax6 increases cortical progenitor proliferation by amounts that vary regionally with normal Pax6 levels. We compared the gene expression profiles of equivalent Pax6-expressing progenitors isolated from Pax6+/+ and Pax6-/- cortices and identified many negatively-regulated cell cycle genes including those encoding Cyclins and Cdks. Biochemical assays indicated that Pax6 directly represses Cdk6 expression. Cyclin/Cdk repression inhibits retinoblastoma protein (pRb) phosphorylation, thereby limiting the transcription of genes directly promoting mitosis, and we showed that Pax6 inhibits pRb phosphorylation and represses several genes involved in DNA replication. Our results indicate that Pax6M-bM-^@M-^Ys modulation of the cell cycles of cortical progenitors is regional and direct. Two condition experiment, Pax6sey/sey vs Pax6+/+ cortical progenitor cells from lateral cortex. 3 biological replicates. Each replicate contains RNA from cells pooled from 4 individual E12.5 embryos
2013-01-31 | E-GEOD-38703 | biostudies-arrayexpress
Project description:Epigenetic factors (EFs) regulate multiple aspects of cerebral cortex development, including proliferation, neuronal differentiation, laminar fate, and regional identity. The same neurodevelopmental processes are also regulated by transcription factors (TFs), notably the Pax6→Tbr2→Tbr1 cascade expressed sequentially in radial glial progenitors, intermediate progenitors, and postmitotic projection neurons, respectively. Here, we studied the EF landscape and its regulation in embryonic mouse neocortex. Microarray and in situ hybridization assays revealed that many EF genes are expressed in specific cortical cell types, such as intermediate progenitors, or in rostrocaudal gradients. Furthermore, many EF genes are directly bound and transcriptionally regulated by Pax6, Tbr2, or Tbr1, as determined by chromatin immunoprecipitation-sequencing and gene expression analysis of TF mutant cortices. The results demonstrated that Pax6, Tbr2, and Tbr1 form a direct feedforward genetic cascade, with direct feedback repression. Results also revealed that each TF regulates multiple EF genes that control DNA methylation, histone marks, chromatin remodeling, and noncoding RNA.
2018-07-30 | GSE115703 | GEO
Project description:The mechanisms by which the early spatiotemporal expression patterns of transcription factors such as Pax6 regulate the region-specific proliferation rates of neural progenitors are poorly understood. Pax6 is expressed in a gradient across the developing cortex and is essential for normal corticogenesis. We found that constitutive or conditional loss of Pax6 increases cortical progenitor proliferation by amounts that vary regionally with normal Pax6 levels. We compared the gene expression profiles of equivalent Pax6-expressing progenitors isolated from Pax6+/+ and Pax6-/- cortices and identified many negatively-regulated cell cycle genes including those encoding Cyclins and Cdks. Biochemical assays indicated that Pax6 directly represses Cdk6 expression. Cyclin/Cdk repression inhibits retinoblastoma protein (pRb) phosphorylation, thereby limiting the transcription of genes directly promoting mitosis, and we showed that Pax6 inhibits pRb phosphorylation and represses several genes involved in DNA replication. Our results indicate that Pax6’s modulation of the cell cycles of cortical progenitors is regional and direct.
2013-01-31 | GSE38703 | GEO
Project description:Pax6 limits the competence of developing cerebral cortical cells
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Project description:The relationships between impaired cortical development and consequent malformations in neurodevelopmental disorders, as well as the genes implicated in these processes, are not fully elucidated to date. In this study, we report six novel cases of patients affected by BBSOAS (Boonstra-Bosch-Schaff Optic Atrophy Syndrome), a newly emerging rare neurodevelopmental disorder, caused by loss-of-function mutations of the transcriptional regulator NR2F1. Young patients with NR2F1 haploinsufficiency display mild to moderate intellectual disability and show reproducible polymicrogyria-like brain malformations in the parietal and occipital cortex. Using a recently established BBSOA mouse model, we found that Nr2f1 regionally controls long-term self-renewal of neural progenitor cells via modulation of cell cycle genes and key cortical development master genes, such as Pax6. In the human foetal cortex, distinct NR2F1 expression levels encompass gyri and sulci and correlate with local degrees of neurogenic activity. In addition, reduced NR2F1 levels in cerebral organoids affect neurogenesis and PAX6 expression. We propose NR2F1 as an area-specific regulator of mouse and human brain morphology and a novel causative gene of abnormal gyrification.
2020-05-06 | GSE146595 | GEO
Project description:Increased cortical size is essential to the enhanced intellectual capacity of primates during mammalian evolution. The mechanisms that control cortical size are largely unknown. Here, we show that mammalian BAF170, a subunit of the chromatin remodeling complex mSWI/SNF, is an intrinsic factor that controls cortical size. We find that the conditional deletion of BAF170 promotes indirect neurogenesis by increasing the pool of intermediate progenitors (IPs) and results in an enlarged cortex, whereas cortex-specific BAF170 over-expression results an opposing phenotype. Mechanistically, BAF170 competes with BAF155 subunit in the BAF complex, affecting the euchromatin structure and thereby modulating the binding efficiency of Pax6/REST-corepressor complex to Pax6 target genes that regulate the generation of IPs and late cortical progenitors. Our findings reveal a molecular mechanism mediated by the mSWI/SNF chromatin-remodeling complex that controls cortical architecture. Cortical gene expression is compared between three E12.5 mouse embryos with cortex-specific loss of BAF170 function and three littermate control embryos.
2013-05-02 | E-GEOD-45629 | biostudies-arrayexpress
Project description:We then examined the mutant mice that lack both Dmrt3 and Dmrta2 alleles, and found the size of the medial cortex including the hippocampus and the cortical hem was significantly reduced in mutant brains .To further investigate how Dmrt3 and Dmrta2 are involved in the development of the medial cortex, we applied gene expression profiling approach using whole genome DNA microarray to identify genes which are differentially expressed in Dmrt3/Dmrta2-knockdown cells. Cortical cells knocked-down both Dmrt3 and Dmrta2 exhibited a dramatic increase of Pax6 expression in the medial cortex, leading to the precocious neuronal differentiation, and simultaneous knockdown of Pax6 with Dmrt3/Dmrta2 rescued the phenotype. Our results unveil a key mechanism that mammalian Dmrt factors maintain more proliferative potential of neural progenitors by suppressing Pax6 expression in the developing cerebral cortex.
2019-08-03 | GSE83639 | GEO
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:Cerebral organoids â three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells â have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. 734 single-cell transcriptomes from human fetal neocortex or human cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Fetal neocortex data were generated at 12 weeks post conception (chip 1: 81 cells; chip 2: 83 cells) and 13 weeks post conception (62 cells). Cerebral organoid data were generated from dissociated whole organoids derived from induced pluripotent stem cell line 409B2 (iPSC 409B2) at 33 days (40 cells), 35 days (68 cells), 37 days (71 cells), 41 days (74 cells), and 65 days (80 cells) after the start of embryoid body culture. Cerebral organoid data were also generated from microdissected cortical-like regions from H9 embryonic stem cell derived organoids at 53 days (region 1, 48 cells; region 2, 48 cells) or from iPSC 409B2 organoids at 58 days (region 3, 43 cells; region 4, 36 cells).
2015-12-07 | E-GEOD-75140 | biostudies-arrayexpress