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GSE25548
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During development, a polarized sheet of epidermal cells undergoes stratification and differentiation to produce the skin barrier. Through mechanisms poorly understood, the process involves adhesion and Notch signaling. To elucidate how epidermal embryogenesis is governed, we conditionally targeted transcription factor serum response factor (SRF), which has been shown to be essential for proper epidermal differentiation in vitro and in vivo. Seeking mechanism, we identified actomyosin-related genes as well-known SRF targets downregulated shortly after ablation. We show that this results in a diminished cortical actomyosin network which fails to regulate the transition of cells from the basal proliferative layer to the suprabasal differentiating layer resulting in an inability of cells to properly execute stratification and differentiation.
Publication Title
Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 82 Downloadable Samples
IlluminaHiSeq2500, IlluminaGenomeAnalyzerIIx
Description
Ventricular chambers are essential for the rhythmic contraction and relaxation that occurs in every hearbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is still poorly understood. Here we show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation and later coordinates ventricular patterning and compaction with coronary vessel development to give rise to the mature chamber via a temporal sequence of ligand signalling determined by the glycosyltransferase Manic Fringe (Mfng). The early endocardial expression of Mfng favours Dll4-Notch1 signalling, Which induces trabeculation in the developing ventricle.Ventricular maturation and compaction in turn require Mfng and Dll4 downregulation in the endocardium, Which allows myocardial Jag1- And Jag2- Signalling to Notch1 in this tissue.Timely and spatial perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies. Overall design: Dll4 and Notch1 conditional KOs using Nfact1 and/or Tie2 driven Cre expression: RNA was isolated from pooled whole hearts of 8 (Nfact1) or 9 (Tie2) E9.5 embryos per replicate. Dll4flox;Nfatc1-Cre and WT siblings (4 KO and 4 WT replicates), Notch1flox;Nfatc1-Cre and WT siblings (3 KO and 2 WT replicates), Dll4flox;Tie2-Cre and WT siblings (3 KO and 3 WT replicates). Jag1, Jag2 and Jag1Jag2 conditional KOs using cTnT driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. Jag1flox;cTnT-Cre and WT siblings (3 KO and 3 WT replicates), Jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). Jag1flox;jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). MFng Gain Of Function using Tie2 driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. MFng;Tie2-Cre and WT siblings (4 GOF and 4 WT replicates). For Dll4, Noth1 and Jag1 KOs, libraries were prepared using the standard Illumina TrueSeq RNASeq library preparation kit and sequenced in a GAIIx Illumina sequencer using a 75bp single end elongation protocol. For Jag2 and Jag1Jag2 KOs and MFng GOF libraries were prepared prepared using the NEBNext Ultra RNA Library Prep Kit for Illumina and sequenced in a HiSeq2500 Illumina sequencer using a 61bp single end elongation protocol
Publication Title
Sequential Notch activation regulates ventricular chamber development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Our studies identify a mechanism of signaling crosstalk during valve morphogenesis that sheds light on the origin of congenital heart defects associated with reduced Notch function. Overall design: Aortic and pulmonary cardiac valves were isolated by laser microdissection from WT and Jag1flox;Nkx2.5-Cre mouse embryos at stage E14.5, and their expression profile characterized by RNA-Seq.
Publication Title
Sequential Ligand-Dependent Notch Signaling Activation Regulates Valve Primordium Formation and Morphogenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2000
Description
Pitx1, critical regulator of a limited hindlimb-specific gene network, targets the limb development program common to both fore- and hindlimbs in order to implement hindlimb-specific limb morphology. Overall design: The gene regulatory networks governing forelimb vs. hindlimb development in mouse were investigated using expressing profiling of morphologically stage-matched e10.5 forelimbs and e11.0 hindlimbs, ChIPseq of chromatin marks, and ChIPseq of limb-specific transcription factors Pitx1 and Tbx5. The makeup of the Pitx1-directed components of the hindlimb gene network were investigated using expression profiling of Pitx1 null hindlimbs at two stages (e11.0 and e11.5).
Publication Title
Regulatory integration of Hox factor activity with T-box factors in limb development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
The combinatorial expression of the Hox genes along the body axes, referred to as the HOX code, is a major determinant of cell fate and plays a prevailing role in generating the animal body plan. In developing limb buds, the paralogous group 13 genes of the HoxA and HoxD clusters are essential for patterning the distal-most limb structures, the digits. Inactivation of HOXA13 and HOXD13 transcription factors (HOX13) leads to complete digit agenesis in mice, but how HOX13 regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here we performed genome-wide profiling of HOX13 by chromatin immunoprecipitation and analyzed the transcriptome and chromatin state of wild type early and late-distal limb buds, as well as Hoxa13-/-;Hoxd13-/- compound mutant limb buds. Our results show that inactivation of HOX13 impairs the activation and repression of putative cis-regulatory modules specific to the late-distal limb cells. Loss of HOX13 also disrupts the specific, spatial patterning of gene expression along the proximal-distal axis of the developing limb buds. These results show that proper termination of the early limb transcriptional program and activation of the late-distal limb program are coordinated by the dual action of HOX13 on cis-regulatory modules. Overall design: Totla mRNAs from dissected distal parts of e11.5 forelimb, of wild-type as well as Hoxa13-/-;Hoxd13-/- mice
Publication Title
Regulatory integration of Hox factor activity with T-box factors in limb development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Left ventricular noncompaction (LVNC) Causes prominent ventricular trabeculations and reduces cardiac systolic function. The clinical presentation of LVNC ranges from asymptomatic to heart failure. We show that germline mutations in human MIB1 (mindbomb homolog 1), which encodes an E3 ubiquitin ligase that promotes endocytosis of the NOTCH ligands DELTA and JAGGED, cause LVNC in autosomal-dominant pedigrees, with affected individuals showing reduced NOTCH1 activity and reduced expression of target genes. Functional studies in cells and zebrafish embryos and in silico modeling indicate that MIB1 functions as a dimer, which is disrupted by the human mutations. Targeted inactivation of Mib1 in mouse myocardium causes LVNC, a phenotype mimicked by inactivation of myocardial Jagged1 or endocardial Notch1. Myocardial Mib1 mutants show reduced ventricular Notch1 activity, expansion of compact myocardium to proliferative, immature trabeculae and abnormal expression of cardiac development and disease genes. These results implicate NOTCH signaling in LVNC and indicate that MIB1 mutations arrest chamber myocardium development, preventing trabecular maturation and compaction. Overall design: RNA was isolated from the ventricles of 16 WT and 16 Mib1flox; CTnT-cre hearts at E14.5 and then pooled into four replicates.
Publication Title
Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The objective of this study was to determine the gene expression changes mediated by the alpha6beta4 integrin using MDA-MB-435 breast carcinoma cell line under normal culturing conditions (10% FCS in DMEM).
Publication Title
Integrin alpha6beta4 controls the expression of genes associated with cell motility, invasion, and metastasis, including S100A4/metastasin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Ragweed challenge in Ragweed (RWE) sensitized animals generates Reactive oxygen species (ROS) in the airway epithelium and induces allergic airway inflammation. We want to study the genes induced by ROS generated by RWE. This goal can be achieved by comparing PBS challenge vs. RWE challenge.
Publication Title
Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This experiment is designed to study the effects to HMPV on A549 over time
Publication Title
Identification of human metapneumovirus-induced gene networks in airway epithelial cells by microarray analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify a cohort of rhythmically expressed genes in the murine Distal Colon,microarrays were used to measure gene expression over a 24-hour light/dark cycle.The rhythmic transcripts were classified according to expression patterns, functions and association with physiological and pathophysiological processes of the colon including motility, colorectal cancer formation and inflammatory bowel disease.
Publication Title
Transcriptional profiling of mRNA expression in the mouse distal colon.
Sample Metadata Fields
No sample metadata fields
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