Expression data (messenger RNA) from developing Neural Tubes of mouse embryos
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE140775 | GEO | 2022/11/13
REPOSITORIES: GEO
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Project description:Morphogenesis of the mammalian neural tube (NT) is reliant on precise, spatio-temporal expression of numerous genes and coordinated interaction of signal transduction and gene regulatory networks, disruption of which may contribute to the etiology of neural tube defects (NTDs). MicroRNAs (miRNAs) as well as their downstream messenger RNA (mRNA) targets are key modulators of cell and tissue differentiation. To define potential roles of miRNAs and mRNAs in development of the murine neural tube (NT), total RNA preparations from gestation day (GD)-8.5, -9.0 and -9.5 (crtitcal period of NT developemnt) mouse embryos were used to hybridize both microRNA arrays and messenger RNA arrays, to identify miRNAs and mRNAs co-expressed in the same developing NT tissue samples.
2022-11-13 | GSE140776 | GEO
Project description:BACKGROUND: Development of the neural tube is a highly orchestrated process relying on precise, spatio-temporal expression of numerous genes as well as hierarchies of signal transduction and gene regulatory networks. Disruption of expression of a number of genes participating in these networks is believed to underlie developmental anomalies such as neural tube defects (NTDs) resulting from anomalous neural tube morphogenesis. MicroRNAs (miRNAs), a large family of noncoding RNAs, have been shown to function as gene silencers, and thus, are key modulators of cell and tissue differentiation. To elucidate potential roles of miRNAs in murine neural tube development, miRNA gene expression profiling has been utilized in the current study, to garner novel and in-depth knowledge on the expression and regulation of genes encoding miRNAs as well as their potential target genes governing maturation of the mammalian neural tube. METHODS: With the aim of identifying differentially expressed miRNAs during mammalian neural tube ontogenesis, miRNA expression profiles from gestation day (GD) -8.5, -9.0 and -9.5 murine neural tube tissue were compared utilizing miRXplore™ microarrays from Miltenyi Biotech GmbH. Gene expression changes observed in microarray analysis were verified by TaqManTM quantitative Real-Time PCR. clValid R package and the UPGMA (hierarchical) clustering method were utilized for cluster analysis of the microarray data. Functional associations among selected miRNAs were examined exploiting Ingenuity Pathway Analysis. RESULTS: Expression of approximately 12% of the 609 murine miRNA genes examined was detected in murine neural tube tissues from GD -8.5, -9.0 and -9.5. Clustering analysis revealed several developmentally regulated clusters among these expressed genes. MicroRNA target analysis enabled identification of a panoply of protein-coding target genes of the differentially expressed miRNAs within such clusters. Interestingly, many of these target genes have been shown to be associated with vital cellular processes such as cell proliferation, cell adhesion, cell migration, differentiation, apoptosis and epithelial-mesenchymal transformation, all of which are essential for normal neural tube development. Utilization of Ingenuity Pathway Analysis (IPA; Ingenuity Systems) allowed identification of interactive biological networks connecting differentially expressed miRNAs and their target genes highlighting functional relationships. CONCLUSIONS: In the present study, a unique gene expression signature of a range of miRNAs in embryonic neural tube tissue was delineated. Analysis of miRNA target genes and gene interaction pathways emphasized that expression of numerous protein-encoding genes, indispensable for normal neural tube morphogenesis, may be regulated by specific miRNAs. Time-course experiment (Developmental Stages), ICR mice embryos on gestational days (GD) 8.5, 9.0 and 9.5. Biological replicates: For each day of gestation, 3 independent pools of 15 to 20 staged embryos were used to procure embryonic orofacial tissues for preparation of 3 distinct pools of RNA that were independently processed and applied to individual miRXplore™ microRNA Microarray chips (Miltenyi Biotec GmbH). Technology: 2-color spotted cDNA, Hy5 (experimental sample) vs. Hy3 (control - miRXplore Universal Reference).
2010-12-01 | E-GEOD-20879 | biostudies-arrayexpress
Project description:BACKGROUND: Development of the neural tube is a highly orchestrated process relying on precise, spatio-temporal expression of numerous genes as well as hierarchies of signal transduction and gene regulatory networks. Disruption of expression of a number of genes participating in these networks is believed to underlie developmental anomalies such as neural tube defects (NTDs) resulting from anomalous neural tube morphogenesis. MicroRNAs (miRNAs), a large family of noncoding RNAs, have been shown to function as gene silencers, and thus, are key modulators of cell and tissue differentiation. To elucidate potential roles of miRNAs in murine neural tube development, miRNA gene expression profiling has been utilized in the current study, to garner novel and in-depth knowledge on the expression and regulation of genes encoding miRNAs as well as their potential target genes governing maturation of the mammalian neural tube. METHODS: With the aim of identifying differentially expressed miRNAs during mammalian neural tube ontogenesis, miRNA expression profiles from gestation day (GD) -8.5, -9.0 and -9.5 murine neural tube tissue were compared utilizing miRXplore™ microarrays from Miltenyi Biotech GmbH. Gene expression changes observed in microarray analysis were verified by TaqManTM quantitative Real-Time PCR. clValid R package and the UPGMA (hierarchical) clustering method were utilized for cluster analysis of the microarray data. Functional associations among selected miRNAs were examined exploiting Ingenuity Pathway Analysis. RESULTS: Expression of approximately 12% of the 609 murine miRNA genes examined was detected in murine neural tube tissues from GD -8.5, -9.0 and -9.5. Clustering analysis revealed several developmentally regulated clusters among these expressed genes. MicroRNA target analysis enabled identification of a panoply of protein-coding target genes of the differentially expressed miRNAs within such clusters. Interestingly, many of these target genes have been shown to be associated with vital cellular processes such as cell proliferation, cell adhesion, cell migration, differentiation, apoptosis and epithelial-mesenchymal transformation, all of which are essential for normal neural tube development. Utilization of Ingenuity Pathway Analysis (IPA; Ingenuity Systems) allowed identification of interactive biological networks connecting differentially expressed miRNAs and their target genes highlighting functional relationships. CONCLUSIONS: In the present study, a unique gene expression signature of a range of miRNAs in embryonic neural tube tissue was delineated. Analysis of miRNA target genes and gene interaction pathways emphasized that expression of numerous protein-encoding genes, indispensable for normal neural tube morphogenesis, may be regulated by specific miRNAs.
2010-12-01 | GSE20879 | GEO
Project description:Background: In the early stage of embryonic development, the neural tube (NT) cannot be closed properly due to some complex factors such as, environmental factors, genetic factors and the relationship between various factors, leading to the occurrence of neural tube defects (NTDs). Methods: In this study, we induced the mouse model of NTDs by feeding mice a low-folate diet and injecting 1.5mg/kg methotrexate on E7.5. Fetal mice were achieved at E13.5, then we extracted proteins from brain tissue with trypsin digestion. After enzymatic digestion, peptides were labeled with TMT/iTRAQ and then separated in high-performance liquid chromatography (HPLC) for subsequent LC-MS/MS analysis. To analyze the functional enrichment of differentially expressed proteins(DEPs) in the NTDs mice tissues with low folate induction, we used Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway annotation to analyze proteomic changes. Results: Low folate induced mouse model was successfully constructed. Folate was used as a sensitizing agent, the teratogenicity rate of the NTDs fetal mice was increased to 36.5% when methotrexate was injected to maternal mice at E7.5. 6614 proteins were identified by mass spectrometry, among them, 5656 proteins were quantified. In the following proteomic analysis, GO classification and KEGG pathway enrichment analysis were conducted, and heatmaps were drawn for differentially expressed proteins(DEPs). Moreover, the main pathways associated with NTDs, such as Hedgehog, Wnt, p53, Hippo signaling pathways, and one carbon pool by folate, can be identified through the generation of a protein-protein interaction (PPI) network. It was also found that the regulation of ribosomal proteins has a certain impact on neural tube development, such as RPL13 and RPL14, which are upregulated in NTDs. Conclusions: Our results revealed proteomic changes in the tissues of low folate induced NTDs mice, as well as validation showed that ribosomal proteins play a regulatory role during the development of NTDs, it provides new ideas for the pathogenesis and preventive measures of NTDs.
2024-03-12 | PXD045752 | Pride
Project description:Background: Although adequate periconceptional folic acid (FA) supplementation has reduced the occurrence of neural tube defects (NTDs)-affected pregnancies, mechanisms underlie FA resistant NTDs are poorly understood, so that NTDs still remain a global public health concern now. It has been proven that high level of Krüppel-like factor 12 (KLF12) has bad effects on heath in most cases, but there is no evidence concerning its roles during development. Methods: We used KLF12-overexpression mice to study the effects of high level of KLF12 on neural tube development. Findings: We showed KLF12-overexpression fetuses died in utero at around 10.5 days post coitus with 100% cranial NTDs. Neither FA or formate benefited normal neural tube closure in mutant fetuses. Further anylasis revealed high level of KLF12 caused NTDs in mice via overactivating Sonic hedgehog (Shh) signaling pathway, leading to upregulation of Ptch1, Gli1, Hhip etc. PF-5274857, an antagonist of Shh signaling pathway could significantly promote dorsolateral hinge point formation and partially rescue the phynotype. Interpretation: The regulatory hierarchy between high level of KLF12 and FA-resistant NTDs might provide new insights for the diagnosis and treatment of unexplained NTDs in the future.
2021-02-04 | GSE166054 | GEO
Project description:Purpose: Identify genes and pathways affected in tuft embryos with NTDs Results: Expression of genes associated with neural tube closure and components of non-canonical WNT signaling/PCP pathways were affected Conclusions: TET1 regulates genes associated with neural tube closure
2016-05-04 | GSE75001 | GEO
Project description:At an incidence of approximately 1/1000 births, neural tube defects (NTDs) comprise one of the most common and devastating congenital disorders. In an attempt to enhance and expand our understanding of neural tube closure, we undertook a high-throughput gene expression analysis of the neural tube as it was forming in the mouse embryo. Open and closed sections of the developing neural tube were micro-dissected from mouse embryos, and hybridized to Affymetrix mouse expression arrays. Clustering of genes differentially regulated in open and closed sections of the developing neural tube highlighted molecular processes previously recognized to be involved in neural tube closure and neurogenesis. Analysis of the genes in these categories identified potential candidates underlying neural tube closure. In addition, we identified approximately 25 novel genes, of unknown function, that were significantly up-regulated in the closed neural tube. Based on their expression patterns in the developing neural tube, five novel genes are proposed as interesting candidates for involvement in neurogenesis. The high-throughput expression analysis of the neural tube as it forms allows for better characterization of pathways involved in neural tube closure and neurogenesis, and hopefully will strengthen the foundation for further research along the pathways dictating neural tube development.
2014-01-01 | GSE39442 | GEO
Project description:Neural tube defects (NTDs) are common birth defects in humans and show an unexplained female bias. Female mice lacking the tumor suppressor p53 display NTDs with incomplete penetrance. We found that the combined loss of pro-apoptotic BIM and p53 caused 100% penetrant, female-exclusive NTDs, which allowed us to investigate the female-specific functions of p53. We report that female p53–/– neural tube samples show fewer cells with inactive X markers Xist and H3K27me3, and a concomitant increase in biallelic expression of the X-linked genes, Huwe1 and Usp9x. The depletion of Xist and increase X-linked gene expression was confirmed by RNA sequencing.
2019-03-26 | GSE127446 | GEO
Project description:Neural Tube Defects (NTDs) are a class of severe congenital developmental defects caused by abnormal closure of the neural tube during early embryonic development, including conditions such as anencephaly, spina bifida, and encephalocele. Currently, NTDs are considered to result from the combined effects of genetic and environmental factors, particularly maternal folate intake during pregnancy, leading to widespread epigenetic dysregulation. However, the role of N6-methyladenine (N6-mA) in embryonic neural development remains largely unknown. Here, we found significant upregulation of Alkbh1 and concomitant significant downregulation of overall 6mA in brain tissue of a mouse model of NTDs. Further investigation through MeDIP, CUT&TAG, and single-cell sequencing revealed crosstalk between N6-mA and H3K9me3-marked heterochromatin, primarily impacting the involvement of embryonic glial cells in the formation of the hindbrain during embryonic neural tube development. These findings collectively suggest a potential epigenetic role of N6-mA in mammalian brain development, potentially exhibiting cell type specificity.
2024-11-28 | GSE268545 | GEO
Project description:To investigate the associated with DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated.
2022-09-20 | GSE204869 | GEO