Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA136675 | ENA |
REPOSITORIES: ENA
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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. 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
2011-01-07 | E-GEOD-26502 | biostudies-arrayexpress
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
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
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 | GSE87652 | GEO
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
Project description:The BMP signaling pathway regulates multiple steps of hematopoiesis, mediated through receptor-regulated Smads, including Smad1 and Smad5. Here we use loss-of-function approaches in zebrafish to compare the roles of Smad1 and Smad5 during embryonic hematopoiesis. Microarray experiments revealed that the two proteins regulate redundantly the key initiators of the hemato-vascular program, including scl, lmo2, and gfi1. However, each also regulates a remarkably distinct genetic program, with Smad5 uniquely regulating the BMP signaling pathway itself. Our results suggest that specificity of BMP signaling output, with respect to hematopoiesis, can be explained by differential functions of Smad1 and Smad5. Keywords: Gene expression transcript profiles
2008-08-22 | GSE8903 | GEO
Project description:The tightly controlled BMP-Smad1 pathway is essential for embryonic development and postnatal tissue homeostasis. Dysfunction of BMP-Smad1 signaling also leads to tumor development such as juvenile polyposis and Cowden syndromes and various tumors in mouse models, with unknown pathological mechanisms. Here we establish a link between the BMP-Smad pathway and the prominent tumor suppressor Atm-p53 pathway. We identify activated nuclear Smad1 as an Atm substrate under genotoxic stress. Atm-mediated Smad1 S239 phosphorylation disrupts Smad1 interaction with protein phosphatase PPM1A and enhances Smad1 activation and up-regulation, which not only turns on target genes including Cdk1nc but also interacts with p53 and inhibits Mdm2-mediated p53 ubiquitination, leading to p53 stabilization. Functionally, Smad1 acts like a tumor suppressor in DNA damage response, cell transformation and tumorigenesis in a p53-dependent manner. Sequencing of the gastric cancer samples revealed that Smad1 is frequently mutated, with S239 as mutational hotspot. This study thus establishes the BMP-Smad1 pathway as an integral part of DNA damage response, which can suppresses tumorigenesis via p53. Transformed MEFs (Smad1f/f, Smad1f/f Cre) treated with 50ng/ml BMP2, 1 ug/ml doxorubincin, or both for different periods of time. The mRNA levels of all genes were compared using microarray analysis.
2012-12-31 | E-GEOD-36843 | biostudies-arrayexpress
Project description:The tightly controlled BMP-Smad1 pathway is essential for embryonic development and postnatal tissue homeostasis. Dysfunction of BMP-Smad1 signaling also leads to tumor development such as juvenile polyposis and Cowden syndromes and various tumors in mouse models, with unknown pathological mechanisms. Here we establish a link between the BMP-Smad pathway and the prominent tumor suppressor Atm-p53 pathway. We identify activated nuclear Smad1 as an Atm substrate under genotoxic stress. Atm-mediated Smad1 S239 phosphorylation disrupts Smad1 interaction with protein phosphatase PPM1A and enhances Smad1 activation and up-regulation, which not only turns on target genes including Cdk1nc but also interacts with p53 and inhibits Mdm2-mediated p53 ubiquitination, leading to p53 stabilization. Functionally, Smad1 acts like a tumor suppressor in DNA damage response, cell transformation and tumorigenesis in a p53-dependent manner. Sequencing of the gastric cancer samples revealed that Smad1 is frequently mutated, with S239 as mutational hotspot. This study thus establishes the BMP-Smad1 pathway as an integral part of DNA damage response, which can suppresses tumorigenesis via p53.
2012-12-31 | GSE36843 | GEO
Project description:Xenopus embryonic ectodermal cells are responsive to various inducing factors. Mesoderm is specified and patterned by extracellular factors including FGF, Nodal, BMP and Wnt families. Pinhead is another secreted protein implicated in mesoderm formation. We found that Pinhead physically interacts with and antagonizes ADMP (anti-dorsalizing morphogenetic protein) that acts as BMP-like protein to promote ventral mesoderm formation. ADMP and BMPs have been shown to cooperate to activate phospho-Smad1 signaling to lead to ventral mesoderm development. Since Chordin is a BMP antagonist, we hypothesized that Pinhead together with Chordin can promote downregulation of phospho-Smad1 signaling that leads to dorsal mesoderm development. RNA sequencing revealed that Pinhead and Chordin synergize in dorsal mesoderm formation in ectodermal explants.
2021-04-19 | GSE168370 | GEO
Project description:BMP (bone morphogenetic protein) signaling plays essential roles in the regulation of early tooth development. It is well acknowledged that with binding of extracellular BMP ligands to the type I and type II transmembrane serine/threonine kinase receptor complexes when triggering of the BMP canonical signaling pathway, receptor activated Smad1/5/8 in cytoplasm bind to Smad4, the central mediator of the canonical BMP signaling pathway, to form transfer complexes for entering the nucleus and regulating target gene expression. However, our recent studies reveal the functional operation of a novel BMP mediated signaling pathway named as the atypical BMP canonical signaling pathway in mouse developing tooth, which is Smad1/5/8 dependent but Smad4 independent. In the current study, we investigated whether this atypical BMP canonical signaling is conserved in human odontogenesis. We showed that pSmad1/5/8 is required for expression of MSX1, a well-defined BMP signaling target gene, in human dental mesenchyme, but the typical BMP canonical signaling is indeed not operating in the early human developing tooth, as assessed by the absence of pSMAD1/5/8-SMAD4 complexes in the dental mesenchyme and expression of MSX1 and translocation of pSMAD1/5/8 induced by BMP4 protein is SMAD4-independent in dental mesenchymal cells. Moreover, RNA-Seq data sets comparing the transcriptome profiles of human dental mesenchymal cells with and without SMAD4 knockdown by siRNA displays unchanged expression profiles of pSMAD1/5/8 downstream target genes, further affirming the functional operation of the atypical canonical BMP signaling pathway in a manner of SMAD1/5/8-dependent but SMAD4-independent in the dental mesenchyme during early odontogenesis.
2021-09-30 | GSE179474 | GEO