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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Smad1 and its target gene Wif1 coordinate BMP and Wnt signaling activities to regulate lung development

ABSTRACT: Bone morphogenetic protein 4 (BMP4) is essential for lung development. To define its intracellular signaling mechanisms by which BMP4 regulates lung development, BMP-specific Smad1 or Smad5 was selectively knocked out in fetal mouse lung epithelial cells. Abrogation of lung epithelial-specific Smad1, but not Smad5, resulted in retardation of lung branching morphogenesis and reduced sacculation, accompanied by altered distal lung epithelial cell proliferation and differentiation, and consequently severe neonatal respiratory failure. By combining cDNA microarray with ChIP-chip analyses, Wnt inhibitory factor-1 (Wif1) was identified as a novel target gene of Smad1 in the developing mouse lung epithelial cells. Loss of Smad1 transcriptional activation of Wif1 expression was associated with reduced Wif1 expression and increased Wnt/beta-catenin signaling activity in lung epithelia, resulting in specific fetal lung abnormalities. Therefore, a novel regulatory loop of BMP4-Smad1-Wif1-Wnt/beta-catenin in coordinating BMP and Wnt pathways to control fetal lung development is suggested. mRNA profiling: Total RNA was isolated from left lobe lungs of three pair of E18.5 wild type and Smad1 lung epithelium-specific conditional knockout mice

ORGANISM(S): Mus musculus

SUBMITTER: Wei Shi

PROVIDER: E-GEOD-26502 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Smad1 and its target gene Wif1 coordinate BMP and Wnt signaling activities to regulate lung development

Project description:Bone morphogenetic protein 4 (BMP4) is essential for lung development. To define its intracellular signaling mechanisms by which BMP4 regulates lung development, BMP-specific Smad1 or Smad5 was selectively knocked out in fetal mouse lung epithelial cells. Abrogation of lung epithelial-specific Smad1, but not Smad5, resulted in retardation of lung branching morphogenesis and reduced sacculation, accompanied by altered distal lung epithelial cell proliferation and differentiation, and consequently severe neonatal respiratory failure. By combining cDNA microarray with ChIP-chip analyses, Wnt inhibitory factor-1 (Wif1) was identified as a novel target gene of Smad1 in the developing mouse lung epithelial cells. Loss of Smad1 transcriptional activation of Wif1 expression was associated with reduced Wif1 expression and increased Wnt/beta-catenin signaling activity in lung epithelia, resulting in specific fetal lung abnormalities. Therefore, a novel regulatory loop of BMP4-Smad1-Wif1-Wnt/beta-catenin in coordinating BMP and Wnt pathways to control fetal lung development is suggested.

2011-01-07 | GSE26502 | GEO

Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration

Project description:This SuperSeries is composed of the following subset Series: GSE29193: Genome-wide location analysis of BMP (SMAD1) in mouse erythroid progenitors co-occupted with lineage specific regulators (GATA1, GATA2) GSE29194: Genome-wide location analysis of WNT (Tcf7l2) and BMP (SMAD1) in human hematopoeitic progenitors co-occupied with lineage specific regulators (GATA1, GATA2) GSE29195: Genome-wide location analysis of WNT (Tcf7l2) and BMP (SMAD1) in human hematopoeitic cell lines co-occupied with lineage specific regulators (GATA1, GATA2, CEBPA) Refer to individual Series

2011-10-06 | E-GEOD-29196 | biostudies-arrayexpress

Genomic integration of Wnt/b-catenin and BMP/Smad1 coordinates the transcriptional program of foregut and hindgut progenitors [RNA-seq]

Project description:Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how they are integrated in the genome is poorly understood. Here we identified the Xenopus foregut and hindgut progenitor transcriptomes, which are largely conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/b-catenin acts as a genome-wide toggle between foregut and hindgut programs. In addition to b-catenin-Tcf promoting hindgut gene transcription, we unexpectedly observed Wnt-repressed foregut genes associated with b-catenin-binding to DNA lacking Tcf motifs, suggesting a novel direct repression. We define how BMP and Wnt signaling are integrated in the genome with Smad1 and β-catenin co-occupying DNA elements associated with hundreds of key regulatory genes. These results extend our understanding of GI organogenesis and how Wnt and BMP may coordinate genomic responses in other contexts.

2017-02-28 | GSE87653 | GEO

Genomic integration of Wnt/b-catenin and BMP/Smad1 coordinates the transcriptional program of foregut and hindgut progenitors [ChIP-seq]

2017-02-28 | GSE87652 | GEO

Mus musculus

Project description:Smad1 and its target gene Wif1 coordinate BMP and Wnt signaling activities to regulate lung development

| PRJNA136675 | ENA

Effect of BMP4 and noggin on gene expression in murine R1 ES cells

Project description:To confirm that the SMAD1/5- and SMAD4-associated genes are direct transcriptional regulators in mESCs in response to BMP, we treated undifferentiated R1 ES cells with BMP4 or with the BMP4 antagonist noggin, which can inhibit BMP signaling effectively for 4 h. Undifferentiated R1 ES cells were treated for 4 h with BMP4 or with the BMP4 antagonist noggin, which can inhibit BMP signaling effectively. Untreated R1 ES cells served as the control.

2010-03-07 | E-GEOD-20527 | biostudies-arrayexpress

Effect of BMP4 and noggin on gene expression in murine R1 ES cells

2010-03-01 | GSE20527 | GEO

BMP4 triggers regulatory circuits specifying the cardiac mesoderm lineage

Project description:Cardiac lineage specification in the mouse is controlled by TGFβ and WNT signaling. From fly to fish, BMP has been identified as an indispensable heart inducer. A detailed analysis of the role of Bmp4 and its effectors Smad1/5, however, was still missing. We show that Bmp4 induces cardiac mesoderm formation in murine embryonic stem cells in vitro. Bmp4 first activates Wnt3 and upregulates Nodal. pSmad1/5 and the WNT effector Tcf3 form a complex, and together with pSmad2/3 activate mesoderm enhancers and Eomes. They then cooperate with Eomes to consolidate the expression of many mesoderm factors, including T. Eomes and T form a positive feedback loop and open additional enhancers regulating early mesoderm genes, including the transcription factor Mesp1 establishing the cardiac mesoderm lineage. In parallel, the neural fate is suppressed. Our data confirm the pivotal role of Bmp4 in cardiac mesoderm formation in the mouse. We describe in detail the consecutive and cooperative actions of three signaling pathways, BMP, WNT and Nodal, and their effector transcription factors, during cardiac mesoderm specification.

2023-05-03 | GSE168580 | GEO

Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo

Project description:To explore the loss of Dullurd function in mouse embryo development, we have performed the Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo. Our findings show that Dullard does not act in concert with BMP4 and Smad1/5/8, whereas loss of Dullard is associated with a reduced level of WNT/Î²-catenin signaling activity, accompanied by elevated expression of Wnt3 and WNT antagonists including Dkk1, Sfrp1 and Sfrp5 in mouse germ cell formation. E7.5 mouse embryos were collected. One Dullard-heterozygous embryo and one Dullard-homozygous embryo were used for the analysis.

2013-03-31 | E-GEOD-39224 | biostudies-arrayexpress

Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo

Project description:To explore the loss of Dullurd function in mouse embryo development, we have performed the Agilent microarray analysis between a Dullard-heterozygous and a Dullard-homozygous E7.5 embryo. Our findings show that Dullard does not act in concert with BMP4 and Smad1/5/8, whereas loss of Dullard is associated with a reduced level of WNT/β-catenin signaling activity, accompanied by elevated expression of Wnt3 and WNT antagonists including Dkk1, Sfrp1 and Sfrp5 in mouse germ cell formation.

2013-03-31 | GSE39224 | GEO

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