Gene profiling on mandibular arches (MdPA1) from Tbx1+/+ and Tbx1-/- mouse embryos
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE30980 | GEO | 2014/05/21
SECONDARY ACCESSION(S): PRJNA146189
REPOSITORIES: GEO
Similar Datasets
Project description:Velo-cardio-facial syndrome/DiGeorge syndrome/22q11.2 deletion syndrome (22q11DS) patients have a submucous cleft palate, velo-pharyngeal insufficiency associated with hypernasal speech, facial muscle hypotonia and feeding difficulties. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on 22q11.2, results in a cleft palate and a reduction or loss of branchiomeric muscles. To identify genes downstream of Tbx1 for myogenesis, gene profiling was performed on mandibular arches (MdPA1) from Tbx1+/+ and Tbx1-/- mouse embryos.
2014-05-21 | GSE35013 | GEO
Project description:Velo-cardio-facial syndrome/DiGeorge syndrome/22q11.2 deletion syndrome (22q11DS) patients have a submucous cleft palate, velo-pharyngeal insufficiency associated with hypernasal speech, facial muscle hypotonia and feeding difficulties. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on 22q11.2, results in a cleft palate and a reduction or loss of branchiomeric muscles. To identify genes downstream of Tbx1 for myogenesis, gene profiling was performed on mandibular arches (MdPA1) from Tbx1+/+ and Tbx1-/- mouse embryos. To obtain enough RNA for microarray hybridization experiments, dissected mandibular arches from three Tbx1+/+ and three Tbx1-/- E9.5 embryos were pooled according to genotype, with three microarrays performed in total per genotype. Affymetrix Mouse Gene ST 1.0 arrays (Affymetrix) were used. Hybridization, washing, staining and scanning were performed in the Genomics Core at Einstein (http://www.einstein.yu.edu/genetics/CoreFacilities.aspx?id=23934) according to the Affymetrix manual.
2014-05-21 | E-GEOD-35013 | biostudies-arrayexpress
Project description:Velo-cardio-facial syndrome/DiGeorge syndrome/22q11.2 deletion syndrome (22q11DS) patients have a submucous cleft palate, velo-pharyngeal insufficiency associated with hypernasal speech, facial muscle hypotonia and feeding difficulties. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on 22q11.2, results in a cleft palate and a reduction or loss of branchiomeric muscles. To identify genes downstream of Tbx1 for myogenesis, gene profiling was performed on mandibular arches (MdPA1) from Tbx1+/+ and Tbx1-/- mouse embryos. To obtain enough RNA for microarray hybridization experiments, dissected mandibular arches from three Tbx1+/+ and three Tbx1-/- E10.5 embryos were pooled according to genotype, with three microarrays performed in total per genotype. The tissue was homogenized in Buffer RLT (QIAGEN). Total RNA was isolated with the RNeasy Micro Kit according to the manufacturer’s protocol. Quality and quantity of total RNA was determined using an Agilent 2100 Bioanalyzer (Agilent) and an ND-1000 Spectrophotometer (NanoDrop), respectively. Biotinylated single-stranded cDNA targets were amplified from 100 nanograms (ng) starting total RNA using the Ovation RNA Amplification System V2 and FL- Ovation cDNA Biotin Module V2 (NuGEN). A total of 3.75 ?g of cDNA from the last step was hybridized to the GeneChip Test3 array (Affymetrix) to test the quality of the labeled target. Nucleic acid samples that passed quality control were then hybridized to the GeneChip Mouse Genome 430 2.0 Arrays (Affymetrix). Hybridization, washing, staining and scanning were performed in the Genomics Core at Einstein (http://www.einstein.yu.edu/genetics/CoreFacilities.aspx?id=23934) according to the Affymetrix manual.
2014-05-21 | E-GEOD-30980 | biostudies-arrayexpress
Project description:Approximately 60-70% of patients with 22q11.2 deletion syndrome (22q11.2DS; velo-cardio-facial syndrome/DiGeorge syndrome) have cardiac outflow tract anomalies including persistent truncus arteriosus (PTA) as the most severe defect. Among the genes in the 22q11.2 region, TBX1, encoding a T-box transcription factor is a major candidate for cardiovascular malformations and its inactivation in mice results in a PTA. To identify novel signaling mechanisms that function downstream, we found that Tbx1 restricts canonical Wnt signaling in the pharyngeal apparatus. To test for tissue specificity within the pharyngeal apparatus, we inactivated Tbx1 in the anterior portion of the secondary heart field (AHF) mesoderm using the Mef2c-AHF-Cre allele and observed a full penetrant PTA (n = 30). Tbx1 promotes progenitor cells but restricts differentiation whereas Wnt signaling, in the AHF, promotes cardiomyocyte differentiation. To determine whether Tbx1 and canonical Wnt signaling act in opposing pathways, both alleles of Tbx1 and one β-catenin allele were inactivated in the AHF and 85% of them (n = 35) showed partial or complete rescue. The antagonistic function of the two pathways was further confirmed by gene expression profiling, indicating that these two pathways provide a key balance in the AHF to prevent premature differentiation of progenitor cells prior to reaching the cardiac outflow tract. We inactivatedTbx1 and beta-catenin allele to identify function of Tbx1 and beta-catenin in the anterior portion of the secondary heart field (AHF) mesoderm. We also inactivated both alleles of Tbx1 and one β-catenin alleles (rescue design) to determine whether Tbx1 and canonical Wnt signaling act in opposing pathways
2016-09-01 | E-GEOD-78125 | biostudies-arrayexpress
Project description:Approximately 60-70% of patients with 22q11.2 deletion syndrome (22q11.2DS; velo-cardio-facial syndrome/DiGeorge syndrome) have cardiac outflow tract anomalies including persistent truncus arteriosus (PTA) as the most severe defect. Among the genes in the 22q11.2 region, TBX1, encoding a T-box transcription factor is a major candidate for cardiovascular malformations and its inactivation in mice results in a PTA. To identify novel signaling mechanisms that function downstream, we found that Tbx1 restricts canonical Wnt signaling in the pharyngeal apparatus. To test for tissue specificity within the pharyngeal apparatus, we inactivated Tbx1 in the anterior portion of the secondary heart field (AHF) mesoderm using the Mef2c-AHF-Cre allele and observed a full penetrant PTA (n = 30). Tbx1 promotes progenitor cells but restricts differentiation whereas Wnt signaling, in the AHF, promotes cardiomyocyte differentiation. To determine whether Tbx1 and canonical Wnt signaling act in opposing pathways, both alleles of Tbx1 and one β-catenin allele were inactivated in the AHF and 85% of them (n = 35) showed partial or complete rescue. The antagonistic function of the two pathways was further confirmed by gene expression profiling, indicating that these two pathways provide a key balance in the AHF to prevent premature differentiation of progenitor cells prior to reaching the cardiac outflow tract.
2016-09-01 | GSE78125 | GEO
Project description:22q11 deletion syndrome (22q11DS) is mainly characterised by cardiovascular, craniofacial, thymic and parathyroid abnormalities. Haploinsufficiency of the transcription factor, TBX1 is considered to be a major underlying cause of these defects. Mice in which Tbx1 has been mutated phenocopy 22q11DS. In order to elucidate the transcriptional pathways regulated by Tbx1, the gene expression profile of Tbx1-lacZ positive cells isolated from E9.5 Df1/Tbx1lacZ embryos (Tbx1-null) were compared to cells isolated from Tbx1+/lacZ (Tbx1-heterozygous) embryos. This analysis has led to a better understanding of the pathways important in pharyngeal and heart development. Experiment design: 3 pools of cells (biological replicates) isolated from Df1/Tbx1lacZ embryos and Tbx1+/lacZ embryos were used for hybridisation onto 6 MOE430 v2 oligonucleotide array chips (Affymetrix), making 12 microarrays in total. Each pool of cells was isolated from at least 8 embryos.
2009-05-30 | E-MEXP-2096 | biostudies-arrayexpress
Project description:Deletion of Tbx1, a member of the T-box transcription factor gene family, results in abnormal epithelial fusion between the palatal shelves and the mandible, which induces cleft palate by inhibiting elevation of the palatal shelves. We used microarrays to determine the downstream genes of Tbx1 during palatogenesis and identified distinct classes of dysregulated genes.
2016-04-20 | GSE79514 | GEO
Project description:Post-myocardial infarction (Post-MI) heart failure is an unanswered clinical challenge. Current immunological intervention trials to reduce MI damage are unsatisfactory. Tbx1, the major 22q11.2 deletion syndrome (22q11.2DS) disease gene, reactivated in cardiac lymphatic endothelial cells (LECs) to promote post-MI repair. Endothelial deletion of Tbx1 deteriorated post-MI cardiac function. To identify the initial endothelial-derived gene expression changes that are responsible for lymphangiogenesis and cell non-autonomous functions towards immune cells after MI, we enriched CD31+ endothelial cells from 5 dpMI Ctrl and Tbx1cko hearts and performed RNA-seq. In conclusion, our findings revealed that Tbx1 can promote lymphangiogenesis and alleviate excessive cardiac inflammation in post MI hearts.
2023-08-28 | GSE137063 | GEO
Project description:Hemizygous microdeletions on chromosome 22q11.2 cause a broad spectrum of congenital cardiovascular and craniofacial anomalies known collectively as DiGeorge Syndrome (DGS) that appear to arise from reduced expression of TBX1, a gene in the typically deleted region. Although mice lacking tbx1 display similar, yet more severe, cardiovascular and craniofacial defects, the mechanisms underlying these devastating phenotypes remain incompletely understood. Here, we report that Tbx1 is required prior to pharyngeal arch development to specify the nkx2.5+ cardiopharyngeal cell lineage that gives rise to the cardiovascular and crainiofacial structures absent in tbx1 null zebrafish. Importantly, the role of Tbx1 during cardiopharyngeal lineage specification is conserved in mammals. Further, we learned that DVR1, the zebrafish homolog of mammalian GDF1/3, functions downstream of Tbx1 for pharyngeal progenitor specification. Together, these studies unveil a new paradigm potentially underlying the cardiovascular and craniofacial defects observed in the DGS population.
2018-07-31 | GSE103120 | GEO
Project description:The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a novel player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.
2012-11-26 | GSE42389 | GEO