Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Stem Cells Dev
2011 Apr 01;204:621-33. doi: 10.1089/scd.2010.0209.
Show Gene links
Show Anatomy links
Dual roles of Oct4 in the maintenance of mouse P19 embryonal carcinoma cells: as negative regulator of Wnt/β-catenin signaling and competence provider for Brachyury induction.
Marikawa Y
,
Tamashiro DA
,
Fujita TC
,
Alarcon VB
.
???displayArticle.abstract???
Transcription factor Oct4 is expressed in pluripotent cell lineages during mouse development, namely, in inner cell mass (ICM), primitive ectoderm, and primordial germ cells. Functional studies have revealed that Oct4 is essential for the maintenance of pluripotency in inner cell mass and for the survival of primordial germ cells. However, the function of Oct4 in the primitive ectoderm has not been fully explored. In this study, we investigated the role of Oct4 in mouse P19 embryonal carcinoma (EC) cells, which exhibit molecular and developmental properties similar to the primitive ectoderm, as an in vitro model. Knockdown of Oct4 in P19 EC cells upregulated several early mesoderm-specific genes, such as Wnt3, Sp5, and Fgf8, by activating Wnt/β-catenin signaling. Overexpression of Oct4 was sufficient to suppress Wnt/β-catenin signaling through its action as a transcriptional activator. However, Brachyury, a key regulator of early mesoderm development and a known direct target of Wnt/β-catenin signaling, was unable to be upregulated in the absence of Oct4, even with additional activation of Wnt/β-catenin signaling. Microarray analysis revealed that Oct4 positively regulated the expression of Tdgf1, a critical component of Nodal signaling, which was required for the upregulation of Brachyury in response to Wnt/β-catenin signaling in P19 EC cells. We propose a model that Oct4 maintains pluripotency of P19 EC cells through 2 counteracting actions: one is to suppress mesoderm-inducing Wnt/β-catenin signaling, and the other is to provide competence to Brachyury gene to respond to Wnt/β-catenin signaling.
???displayArticle.pubmedLink???
21083502
???displayArticle.pmcLink???PMC3112048 ???displayArticle.link???Stem Cells Dev ???displayArticle.grants???[+]
Aoki,
Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene.
2007,
Pubmed
Arnold,
Brachyury is a target gene of the Wnt/beta-catenin signaling pathway.
2000,
Pubmed
Badiani,
Dominant interfering alleles define a role for c-Myb in T-cell development.
1994,
Pubmed
Beck,
Expression of Cdx-2 in the mouse embryo and placenta: possible role in patterning of the extra-embryonic membranes.
1995,
Pubmed
Ben-Haim,
The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4.
2006,
Pubmed
Boyer,
Core transcriptional regulatory circuitry in human embryonic stem cells.
2005,
Pubmed
Brennan,
Nodal signalling in the epiblast patterns the early mouse embryo.
2001,
Pubmed
Brocard,
A chimeric Cre recombinase inducible by synthetic,but not by natural ligands of the glucocorticoid receptor.
1998,
Pubmed
Brons,
Derivation of pluripotent epiblast stem cells from mammalian embryos.
2007,
Pubmed
Cao,
POU-V factors antagonize maternal VegT activity and beta-Catenin signaling in Xenopus embryos.
2007,
Pubmed
,
Xenbase
Ciruna,
Expression of the T-box gene Eomesodermin during early mouse development.
1999,
Pubmed
,
Xenbase
Crossley,
The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo.
1995,
Pubmed
Ding,
Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo.
1998,
Pubmed
Gianakopoulos,
Hedgehog signaling induces cardiomyogenesis in P19 cells.
2005,
Pubmed
Han,
Functional domains of the Drosophila Engrailed protein.
1993,
Pubmed
Hanna,
Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo.
2002,
Pubmed
Hao,
WNT/beta-catenin pathway up-regulates Stat3 and converges on LIF to prevent differentiation of mouse embryonic stem cells.
2006,
Pubmed
Harrison,
Sp5, a new member of the Sp1 family, is dynamically expressed during development and genetically interacts with Brachyury.
2000,
Pubmed
Hochedlinger,
Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues.
2005,
Pubmed
Hollenberg,
Use of a conditional MyoD transcription factor in studies of MyoD trans-activation and muscle determination.
1993,
Pubmed
Huelsken,
Requirement for beta-catenin in anterior-posterior axis formation in mice.
2000,
Pubmed
Jaynes,
Active repression of transcription by the engrailed homeodomain protein.
1991,
Pubmed
Jennings,
The Groucho/TLE/Grg family of transcriptional co-repressors.
2008,
Pubmed
Jin,
Identification of an OCT4 and SRY regulatory module using integrated computational and experimental genomics approaches.
2007,
Pubmed
Jones-Villeneuve,
Retinoic acid induces embryonal carcinoma cells to differentiate into neurons and glial cells.
1982,
Pubmed
Kanamori,
The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.
2003,
Pubmed
Kawano,
Secreted antagonists of the Wnt signalling pathway.
2003,
Pubmed
,
Xenbase
Kehler,
Oct4 is required for primordial germ cell survival.
2004,
Pubmed
Kikuchi,
Roles of Axin in the Wnt signalling pathway.
1999,
Pubmed
Kolm,
Efficient hormone-inducible protein function in Xenopus laevis.
1995,
Pubmed
,
Xenbase
Kong,
Expression of Scl in mesoderm rescues hematopoiesis in the absence of Oct-4.
2009,
Pubmed
Korinek,
Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
1997,
Pubmed
Liu,
Requirement for Wnt3 in vertebrate axis formation.
1999,
Pubmed
Loh,
The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.
2006,
Pubmed
Maniatis,
A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways.
1999,
Pubmed
Marikawa,
Wnt/beta-catenin signaling and body plan formation in mouse embryos.
2006,
Pubmed
,
Xenbase
Marikawa,
Aggregated P19 mouse embryonal carcinoma cells as a simple in vitro model to study the molecular regulations of mesoderm formation and axial elongation morphogenesis.
2009,
Pubmed
Morrison,
Conserved roles for Oct4 homologues in maintaining multipotency during early vertebrate development.
2006,
Pubmed
,
Xenbase
Murphy,
Differentiating embryonic stem cells: GAPDH, but neither HPRT nor beta-tubulin is suitable as an internal standard for measuring RNA levels.
2002,
Pubmed
Nichols,
Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.
1998,
Pubmed
Niwa,
Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation.
2005,
Pubmed
Niwa,
How is pluripotency determined and maintained?
2007,
Pubmed
Niwa,
Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.
2000,
Pubmed
Niwa,
Phenotypic complementation establishes requirements for specific POU domain and generic transactivation function of Oct-3/4 in embryonic stem cells.
2002,
Pubmed
Ogawa,
Synergistic action of Wnt and LIF in maintaining pluripotency of mouse ES cells.
2006,
Pubmed
Okamoto,
A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells.
1990,
Pubmed
Okamura,
Requirement of Oct3/4 function for germ cell specification.
2008,
Pubmed
Pesce,
Oct-4: control of totipotency and germline determination.
2000,
Pubmed
Pesce,
Oct-4: gatekeeper in the beginnings of mammalian development.
2001,
Pubmed
Ridgeway,
Wnt signaling regulates the function of MyoD and myogenin.
2000,
Pubmed
Rodda,
Transcriptional regulation of nanog by OCT4 and SOX2.
2005,
Pubmed
Rosner,
A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo.
1990,
Pubmed
Sadowski,
GAL4-VP16 is an unusually potent transcriptional activator.
1988,
Pubmed
Sato,
Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor.
2004,
Pubmed
Schöler,
New type of POU domain in germ line-specific protein Oct-4.
1990,
Pubmed
Sharov,
Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data.
2008,
Pubmed
Singla,
wnt3a but not wnt11 supports self-renewal of embryonic stem cells.
2006,
Pubmed
Strizzi,
Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis.
2005,
Pubmed
Strumpf,
Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst.
2005,
Pubmed
Tago,
Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
2000,
Pubmed
,
Xenbase
Takahashi,
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
2006,
Pubmed
Takao,
Beta-catenin up-regulates Nanog expression through interaction with Oct-3/4 in embryonic stem cells.
2007,
Pubmed
Takemaru,
Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway.
2003,
Pubmed
Tamai,
LDL-receptor-related proteins in Wnt signal transduction.
2000,
Pubmed
,
Xenbase
Tamashiro,
Ectopic expression of mouse Sry interferes with Wnt/beta-catenin signaling in mouse embryonal carcinoma cell lines.
2008,
Pubmed
Tesar,
New cell lines from mouse epiblast share defining features with human embryonic stem cells.
2007,
Pubmed
Triezenberg,
Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression.
1988,
Pubmed
Wu,
GSK3: a multifaceted kinase in Wnt signaling.
2010,
Pubmed
Yamaguchi,
Brachyury (T) expression in embryonal carcinoma P19 cells resembles its expression in primitive streak and tail-bud but not that in notochord.
1999,
Pubmed
Yamaguchi,
T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification.
1999,
Pubmed
Yeom,
Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells.
1996,
Pubmed
Ying,
BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3.
2003,
Pubmed
Yuan,
Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3.
1995,
Pubmed
Zimmerman,
The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4.
1996,
Pubmed
,
Xenbase
van Amerongen,
Towards an integrated view of Wnt signaling in development.
2009,
Pubmed
