In line with our ancestors: Oct-4 and the mammalian germ
BioEssaysPublished 7 December 1998
Maurizio Pesce, Michael Groß, Hans R. Schöler
Citations222
SJR quartileQ1
SJR score1.30
SNIP0.82
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
Abstract
The transcription factor Oct-4 is expressed specifically in the totipotent germline cycle of mice. Cells that lose Oct-4 differentiate along different paths to form embryonic and extraembryonic somatic tissue. Oct-4 may maintain the potency of stem and germline cells by preventing all other differentiation pathways. Oct-4 may also regulate the molecular differentiation of cells in the germ lineage as it progresses from the fertilized egg, through cleavage stage/morula blastomeres, blastocyst, inner cell mass, epiblast, germ cells, and gametes. The factors that regulate, and are regulated by, Oct-4 are reviewed with respect to the phenomena of cell potency and germ/soma segregation and differentiation.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
DevelopmentTemporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development
1,090 Citations1987Marilyn Monk, Michael Boubelı́k +1 more
Stage- and tissue-specific global demethylation and remethylation occurring during embryonic development are shown and it is proposed that much of the methylation observed in somatic tissues acts to stabilize and reinforce prior events that regulate the activity of specific genes, chromosome domains or the X chromosome.
CellRegulatory Mechanisms in Stem Cell Biology
1,057 Citations1997Sean J. Morrison, Nirao M. Shah +1 more
A minimalist definition is that stem cells have the capacity both to self-renew and to generate differentiated progeny, which immediately highlights some important problems.
DevelopmentPrimordial germ cells in the mouse embryo during gastrulation
1,007 Citations1990Malka Ginsburg, Michael Snow +1 more
DevelopmentGermline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells
873 Citations1996Young Il Yeom, Guy Fuhrmann +6 more
Oct-4 expression in the germline is regulated separately from epiblast expression, and this provides the first marker for the identification of totipotent cells in the embryo, and suggests that expression of Oct-4 in the Totipotent cycle is dependent on a set of factors unique to the germ line.
Genes & DevelopmentDevelopmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3.
749 Citations1995Hushan Yuan, Nicoletta Corbi +2 more
FGF-4 is identified as the first known embryonic target gene for Oct-3 and for any of the Sox factors, and insights into the mechanisms of selective gene activation by Sox and octamer-binding proteins during embryogenesis are offered.
ScienceRequirement of FGF-4 for Postimplantation Mouse Development
743 Citations1995Benjamin Feldman, William Poueymirou +3 more
Embryos homozygous for the null allele underwent uterine implantation and induced uterine decidualization but did not develop substantially thereafter, and growth and differentiation of the inner cell mass were rescued when null embryos were cultured in the presence of FGF-4 protein.
DevelopmentForebrain and midbrain regions are deleted in <i>Otx2</i>−/− mutants due to a defective anterior neuroectoderm specification during gastrulation
708 Citations1995Dario Acampora, Sylvie Mazan +5 more
It is suggested that Otx2 expression in endomesoderm and ectoderm is required for anterior neuroectoderm specification, and in gastrulating heterozygous embryos, a post-transcriptional repression acts on lacZ transcripts in the ectodermal layer, but not in the external layer, suggesting that different post- transcriptional mechanisms control Otx1 expression in both layers.
Mechanisms of DevelopmentMouse gastrulation: the formation of a mammalian body plan
623 Citations1997Patrick Tam, Richard Behringer
The mouse embryo before and during gastrulation is explored, highlighting its similarities with other vertebrate embryos and its unique characteristics.
Developmental BiologyOct-4 Transcription Factor Is Differentially Expressed in the Mouse Embryo during Establishment of the First Two Extraembryonic Cell Lineages Involved in Implantation
616 Citations1994Susan L. Palmieri, W Kinyanjui Peter +2 more
The presence of Oct-4 protein in cultured cells and murine embryos as determined by immunohistochemistry using confocal microscopy and a striking difference was seen in primitive endoderm cells which had begun to differentiate and migrate along the inner surface of the trophectoderm.
The EMBO JournalOct‐4: a germline‐specific transcription factor mapping to the mouse t‐complex.
589 Citations1990Hans R. Schöler, Gregory R. Dressler +3 more
It is shown that the ectopic expression of Oct‐4 in HeLa cells is sufficient for transcriptional activation from the octamer motif, indicating thatOct‐4 is a transcription factor that is specifically expressed in cells participating in the generation of the germline lineage.
Current BiologyAnterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo
554 Citations1996Paul Q. Thomas, Rosa Beddington
It is proposed that primitive endoderm is responsible for the initial induction of rostral identity in the embryo, and in particular for the correct definition of the future prosencephalic neurectoderm.
DevelopmentProliferation and migration of primordial germ cells during compensatory growth in mouse embryos
553 Citations1981Patrick Tam, Michael Snow
Primitive-streak-stage mouse embryos treated with Mitomycin C injected intraperitoneally into pregnant females showed impaired fertility and poor breeding performance, mainly caused by a severe reduction of the primordial germ cell population in early embryonic life.
Development<i>Hex</i>: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors
530 Citations1998Paul Q. Thomas, Angus M. Brown +1 more
Hex expression indicates that the anteroposterior axis of the mouse embryo develops from conversion of a proximodistal asymmetry established in the primitive endoderm lineage and its expression within the gut strongly suggests that the ventral foregut is derived from the most anterior definitiveEndoderm and that the liver is probably the most posterior gut derivative.
Mechanisms of DevelopmentDifferential expression of the Oct-4 transcription factor during mouse germ cell differentiation
483 Citations1998Maurizio Pesce, Xiangyuan Wang +2 more
Evidence is provided that Oct-4 undergoes downregulation during oogenesis and spermatogenesis, coincident with entry into meiosis, and analysis of maturation stages of oocytes showed thatOct-4 is upregulated de novo in the final stages of meiotic prophase I in female germ cells, suggesting one of the molecular triggers involved in the commitment to meiosis.
Developmental BiologyThe Allocation of Epiblast Cells to Ectodermal and Germ-Line Lineages Is Influenced by the Position of the Cells in the Gastrulating Mouse Embryo
388 Citations1996Patrick Tam, Sheila X. Zhou
The adoption of developmental fate that is typical of the cell population at the site of transplantation suggests that the specification of cell lineages is subject to certain site-specific influences in the epiblast.
Development<i>nodal</i> expression in the primitive endoderm is required for specification of the anterior axis during mouse gastrulation
387 Citations1997Isabelle Varlet, Jérôme Collignon +1 more
It is concluded that the action of nodal, a TGFbeta-related growth factor expressed in the primitive endoderm, is critical for patterning of the anterior aspects of the A-P axis.
Trends in GeneticsOctamania: The POU factors in murine development
372 Citations1991Hans R. Schöler
The POU family is a group of related transcription factors containing a particular type of bipartite DNA-binding domain that may regulate early events of murine development.
Molecular and Cellular BiologySynergistic Activation of the Fibroblast Growth Factor 4 Enhancer by Sox2 and Oct-3 Depends on Protein-Protein Interactions Facilitated by a Specific Spatial Arrangement of Factor Binding Sites
368 Citations1997Davide-Carlo Ambrosetti, Claudio Basilico +1 more
It is demonstrated that increasing the distance between the octamer and Sox binding sites by base pair insertion results in a loss of enhancer function, which defines one parameter that is fundamental to synergistic activation by Sox2 and Oct-3 and further emphasize the critical role of enhancers DNA sequences in the proper assembly of functional activation complexes.
Trends in GeneticsDNA methylation and imprinting: why bother?
365 Citations1997Rudolf Jaenisch
It is proposed that DNA methylation is only important for the somatic lineages, but has no role in embryonic lineages including the germ line, suggesting imprinting having no intrinsic role in mammalian development.
Developmental BiologyEntry of Mouse Embryonic Germ Cells into Meiosis
351 Citations1997Anne McLaren, D. Southee
It is concluded that the male genital ridge at about 12 dpc produces a factor that inhibits entry of germ cells into meiosis, and that production of this factor is disrupted by prior disaggregation of the genital ridge.
Current Opinion in Cell BiologyCadherins and catenins in development
349 Citations1996Otmar Huber, Christiane Bierkamp +1 more
In a working hypothesis, signaling via beta-catenin regulates the epithelial-mesenchymal transition in vertebrate development.
NatureThe PIE-1 protein and germline specification in C. elegans embryos
340 Citations1996Craig C. Mello, Charlotte Schubert +4 more
It is shown that pie-1 encodes a nuclear protein, PIE-1, that is localized to the germline blastomeres throughout early development and provides an example of a repressor-based mechanism for preserving pluripotency within a stem cell lineage.
NatureRepression of gene expression in the embryonic germ lineage of C. elegans
316 Citations1996Géraldine Seydoux, Craig C. Mello +4 more
It is shown that after each asymmetrical division, embryonically transcribed RNAs are detected in somatic, but not germline, blastomeres, and that germ-cell fate depends on an inhibitory mechanism that blocks new gene expression in the early embryonic germ lineage.
Nucleic Acids ResearchHuman Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues
286 Citations1992Jun Takeda, Susumu Seino +1 more
The isolation of cDNAs encoding Oct3 revealed the expression of two isoforms of this transcription factor termed Oct3A and Oct3B that are generated by alternative splicing that will facilitate genetic studies of this gene.
Annual Review of Cell and Developmental BiologyGERM CELL DEVELOPMENT IN <i>DROSOPHILA</i>
241 Citations1996Anne Williamson, Ruth Lehmann
This review addresses various aspects of germ cell development in Drosophila, such as germ cell determination, germ cell migration, gonad formation, sex determination, and gametogenesis.
Developmental BiologyThe Ligand of the c-kit Receptor Promotes Oocyte Growth
238 Citations1994Alan Packer, Ying Hsu +2 more
It is demonstrated that c-kit and KL are required for maintenance of oocyte growth in vitro and on the regulation of KL production in granulosa cells.
DevelopmentMesP1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation
238 Citations1996Yumiko Saga, Naomi Hata +4 more
The amino acid sequence and its expression pattern suggest that MesP1 plays an important role in the development of the nascent mesoderm including PGC, which is similar to that of PGC detected by the alkaline phosphatase activity.
CellA nexus between Oct-4 and E1 A: Implications for gene regulation in embryonic stem cells
191 Citations1991Hans R. Schöler, Thomas Ciesiolka +1 more
The results indicate that E1A can serve as a bridging factor between Oct-4 and the basal initiation complex, and it is postulated that an E 1A-like factor acts as a cellular bridging factors of Oct- 4 in pluripotent cells.
The EMBO JournalThe oct3 gene, a gene for an embryonic transcription factor, is controlled by a retinoic acid repressible enhancer.
177 Citations1991Hitoshi Okazawa, Koji Okamoto +6 more
It is suggested that RARE1 is a critical cis element for oct3 gene expression in embryonic stem cells and for the RA‐mediated repression.
DevelopmentExpression and function of FGF-4 in peri-implantation development in mouse embryos
175 Citations1994Daniel A. Rappolee, Claudio Basilico +2 more
Findings indicate that FGF-4 produced by undifferentiated ICM cells acts in the peri-implantation period of embryogenesis to influence the production and behavior of endoderm cells derived from them.
Developmental BiologyInactivation of the FGF-4 Gene in Embryonic Stem Cells Alters the Growth and/or the Survival of Their Early Differentiated Progeny
129 Citations1997Phillip J. Wilder, David L. Kelly +7 more
The studies described in this report indicate that certain lineages formed in vitro are affected by the inactivation of the FGF-4 gene, in particular specific cells that form during the initial stage of ES cell differentiation.
Molecular and Cellular BiologyRetinoic acid represses Oct-3/4 gene expression through several retinoic acid-responsive elements located in the promoter-enhancer region.
111 Citations1994Eli Pikarsky, Hava Sharir +2 more
The EMBO JournalRetinoic acid‐mediated down‐regulation of Oct3/4 coincides with the loss of promoter occupancy in vivo.
101 Citations1996Saverio Minucci, V. Botquin +7 more
The partial factor displacement seen in F9 EC cells, combined with the observation that EC and ES cells utilize the proximal and distal enhancers in differential manner, indicate the complex pattern of Oct3/4 gene regulation, which could reflect a cell type‐ and lineage‐specific expression of the gene in vivo.
Mechanisms of DevelopmentStructure, expression and chromosomal location of the Oct-4 gene
99 Citations1991YOUNGILYEOM, Hyekyung Ha +3 more
The genomic structure and sequence ofOct-4 determined in t-haplotypes reveals five exons, and shows no significant changes in the t12 mutant haplotype making it unlikely that Oct-4 and the t 12 early embryonic lethal are the same gene.
Molecular and Cellular BiologyThe Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain
99 Citations1997Alexander Brehm, Kazuyuki Ohbo +1 more
Phosphopeptide analysis revealed that the cell-type-specific difference of C-domain activity correlates with a difference in Oct-4 phosphorylation status, suggesting an additional regulatory mechanism for determiningOct-4 function in rapidly changing cell types during development.
Nature GeneticsMethylation of CpG sites of two X–linked genes coincides with X–inactivation in the female mouse embryo but not in the germ line
92 Citations1992Mark Grant, Maurizio Zuccotti +1 more
In female primordial germ cells, the inactive X chromosome escapes methylation; this may underly the reversibility of inactivation at meiosis, and the imprint specifying preferential X–inactivation in extra–embryonic tissues must reside elsewhere.
Molecular and Cellular BiologyExpression of the K-fgf proto-oncogene is controlled by 3' regulatory elements which are specific for embryonal carcinoma cells.
92 Citations1990Anna Maria Curatola, Claudio Basilico
Nucleic Acids ResearchRegulation of the<i>Oct-4</i>gene by nuclear receptors
88 Citations1994Ian Sylvester, Hans R. Schöler
Binding and transient transfection assays reveal thatOct-4 is subject to negative regulation by different members of the steroid-thyroid hormone receptor superfamily, and important roles for ARP-1 and RAR in Oct-4 expression are indicated.
Mechanisms of DevelopmentThe c-kit receptor is involved in the adhesion of mouse primordial germ cells to somatic cells in culture
85 Citations1997Maurizio Pesce, Anna Di Carlo +1 more
It is demonstrated that SCF/c-kit interaction contributes to the adhesion of primordial germ cells to somatic cells in culture and suggested that the role played by SCF in promoting survival, proliferation and migration of these cells in vitro and in vivo might depend on the ability of the membrane-bound form of this cytokine to directly mediate primordial Germ cell adhesion to the surrounding somatic Cells.
Molecular and Cellular BiologyExtinction of Oct-3/4 gene expression in embryonal carcinoma x fibroblast somatic cell hybrids is accompanied by changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream region.
75 Citations1993E Ben-Shushan, Eli Pikarsky +2 more
Development Genes and EvolutionThe induction of the primordial germ cells in the urodeles
73 Citations1974Lien A. Sutasurja, P. D. Nieuwkoop
It is very likely that in urodeles the primordial germ cells do not arise from predetermined elements such as those demonstrated in anurans, but develop from common, totipotent animal ectodermal cells.
The EMBO JournalHybrid cell extinction and re‐expression of Oct‐3 function correlates with differentiation potential.
73 Citations1993Takuya Shimazaki, Hitoshi Okazawa +6 more
The close correlation between the phenotypic changes and the gain/loss ofOct‐3 function indicates that Oct‐3 can induce dedifferentiation of the neural cells.
AndrologiaDevelopment of primordial germ cells in the mouse*
71 Citations2009Anne McLaren
Germ cell counts over the 7–8 d period of gastrulation have been made, which are consistent with either of two models: derivation of the germ cell lineage from a very small stem cell pool, followed by a constant rate of proliferation, and derivation from a larger initial stem cell Pool, following a period when germ cells are differentiating but not dividing.
The EMBO JournalExcision of the Drosophila transposable element mariner: identification and characterization of the Mos factor.
71 Citations1988Meetha Medhora, A. H. MacPeek +1 more
Genetic and molecular evidence presented in this paper demonstrate that the Mos factor for inherited mosaicism is a special copy of the transposable element mariner, a copy of mariner present at a particular site in a Mos strain shown to be missing in derived strains in which theMos factor has been lost, and in strains with putative transpositions.
Developmental BiologyIsolation of polar granules and the identification of polar granule-specific protein
67 Citations1978Gail L. Waring, C. David Allis +1 more
A basic protein with a molecular weight on SDS-polyacrylamide gels of 95,000 daltons that is unique to embryonic cell populations containing pole cells and is the only major protein species present in preparations in which polar granules are the major morphological constituent.
Molecular EndocrinologySilencing of the Gene for the α-Subunit of Human Chorionic Gonadotropin by the Embryonic Transcription Factor Oct-3/4
66 Citations1997Limin Liu, Douglas W. Leaman +2 more
It is suggested that silencing of Oct-3/4 in trophectoderm is a prerequisite for hCG up-regulation in early human embryos at the time of maternal recognition of pregnancy.
DevelopmentRelocation and reorganization of germ plasm in <i>Xenopus</i> embryos after fertilization
61 Citations1988R. E. Ressom, K. E. Dixon
In the unfertilized egg, germ plasm is widely distributed throughout the vegetal subcortex in small islets, and following fertilization or artificial activation, the location and organization changes, and by the 4- to 8-cell stage the germ Plasm forms a small number of large patches overlying the Vegetal pole.
DevelopmentA study of meiosis in chimeric mouse fetal gonads
40 Citations1990Susanna Dolci, Massimo De Felici
The results support the existence of a meiosis-preventing substance or a factor causing oocyte degeneration in the fetal mouse testis, but not of ameiosis-inducing substance in the Fetal ovary.
Seminars in Developmental BiologyGermline and soma: interactions during early mouse development
26 Citations1994Anne McLaren
The somatic development of the ovary appears more affected by the absence of germ cells than is the testis, and some factor emanating from testicular somatic tissue inhibits germ cells from entering meiosis before birth and thus induces them to embark on spermatogenesis rather than oogenesis.
PubMedCharacterization of the promoter of the proto-oncogene c-kit.
7 Citations1995Tang‐Yuan Chu, Peter Besmer
A unique promoter of the c-kit gene is revealed and provides a basis for further elucidation of the regulatory mechanism of c-Kit gene expression.