Activins are expressed in preimplantation mouse embryos and in ES and EC cells and are regulated on their differentiation

Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 711-723 ◽  
Author(s):  
R.M. Albano ◽  
N. Groome ◽  
J.C. Smith
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Alpha Subunit ◽  
Beta Subunits ◽  
Mouse Development ◽  
Cell Stage ◽  
Mammalian Embryo ◽  
Mesoderm Formation ◽  
Ec Cells ◽  
Early Mouse

Members of the activin family have been suggested to act as mesoderm-inducing factors during early amphibian development. Little is known, however, about mesoderm formation in the mammalian embryo, and as one approach to investigating this we have studied activin expression during early mouse development. Activins are homo- or heterodimers of the beta A or beta B subunits of inhibin, itself a heterodimer consisting of one of the beta subunits together with an alpha subunit. Our results indicate that the oocyte contains mRNA encoding all three subunits, and antibody staining demonstrates the presence of both alpha and beta protein chains. From the fertilized egg stage onwards, alpha subunit protein cannot be detected, so the presence of beta subunits reflects the presence of activin rather than inhibin. Maternal levels of activin protein decline during early cleavage stages but increase, presumably due to zygotic transcription (see below), in the compacted morula. By 3.5 days, only the inner cell mass (ICM) cells of the blastocyst express activin, but at 4.5 days the situation is reversed; activin expression is confined to the trophectoderm. Using reverse transcription-PCR, neither beta A nor beta B mRNA was detectable at the two-cell stage but transcripts encoding both subunits were detectable at the morula stage, with beta B mRNA persisting into the blastocyst. We have also analyzed activin and inhibin expression in ES and EC cells. Consistent with the observation that activins are expressed in the ICM of 3.5-day blastocysts, we find high levels of beta A and beta B mRNA in all eight ES cell lines tested. F9 EC cells express only activin beta B, together with low levels of the inhibin alpha chain. When ES and EC cells are induced to differentiate, levels of activin fall dramatically. These results are consistent with a role for activins in mesoderm formation and other steps of early mouse development.

scholarly journals G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Jan J Zylicz ◽  
Maud Borensztein ◽  
Frederick CK Wong ◽  
Yun Huang ◽  
Caroline Lee ◽  
...  
Keyword(s):  
Cell Fate ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Blastocyst Stage ◽  
Vital Role ◽  
Mouse Development ◽  
Cell Stage ◽  
Developmental Progression ◽  
Early Mouse ◽  
The Impact

Early mouse development is regulated and accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2). Previously, we provided insights into its role in post-implantation development (Zylicz et al., 2015). Here we explore the impact of depleting the maternally inherited G9a in oocytes on development shortly after fertilisation. We show that G9a accumulates typically at 4 to 8 cell stage to promote timely repression of a subset of 4 cell stage-specific genes. Loss of maternal inheritance of G9a disrupts the gene regulatory network resulting in developmental delay and destabilisation of inner cell mass lineages by the late blastocyst stage. Our results indicate a vital role of this maternally inherited epigenetic regulator in creating conducive conditions for developmental progression and on cell fate choices.

Expression of inhibin subunits and follistatin during postimplantation mouse development: decidual expression of activin and expression of follistatin in primitive streak, somites and hindbrain

Development ◽  
1994 ◽  
Vol 120 (4) ◽  
pp. 803-813 ◽  
Author(s):  
R.M. Albano ◽  
R. Arkell ◽  
R.S. Beddington ◽  
J.C. Smith
Keyword(s):  
Primitive Streak ◽  
Beta Subunits ◽  
Single Chain ◽  
Mouse Development ◽  
Mammalian Embryo ◽  
Mesoderm Formation ◽  
B Subunits ◽  
Inducing Factors ◽  
Early Mouse ◽  
Mesoderm Inducing Factors

Members of the activin family are believed to act as mesoderm-inducing factors during early amphibian development. Little is known, however, about mesoderm formation in the mammalian embryo, and as one approach to investigating this we have studied activin and follistatin expression during early mouse development. Activins are homo- or heterodimers of the beta A or beta B subunits of inhibin, itself a heterodimer consisting of one of the beta subunits together with an alpha subunit. Follistatin is a single-chain polypeptide which inhibits activin function. Expression of the inhibin alpha chain could not be detected in embryonic or extraembryonic tissues at any of the stages studied (5.5 to 8.5 days) and expression of the beta A and beta B subunits could only be observed in the deciduum in cells surrounding the embryo. Expression of follistatin could also be detected in the deciduum, but in a pattern complementary to that of the beta subunits. Embryonic expression of follistatin first occurred in the primitive streak, and at later stages transcripts were detectable in the somites and in rhombomeres 2, 4 and 6 of the hindbrain. These results are consistent with a role for activin in mesoderm formation in the mouse embryo, and suggest functions for follistatin in addition to its role as an inhibitor of activin.

A novel H+ permeability dominating intracellular pH in the early mouse embryo

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1353-1361
Author(s):  
J.M. Baltz ◽  
J.D. Biggers ◽  
C. Lechene
Keyword(s):  
Plasma Membrane ◽  
Intracellular Ph ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Types ◽  
Preimplantation Embryos ◽  
Developmentally Regulated ◽  
Cell Stage ◽  
K Concentration ◽  
Early Mouse

Most cell types are relatively impermeant to H+ and are able to regulate their intracellular pH by means of plasma membrane proteins, which transport H+ or bicarbonate across the membrane in response to perturbations of intracellular pH. Mouse preimplantation embryos at the 2-cell stage, however, do not appear to possess specific pH-regulatory mechanisms for relieving acidosis. They are, instead, highly permeable to H+, so that the intracellular pH in the acid and neutral range is determined by the electrochemical equilibrium of H+ across the plasma membrane. When intracellular pH is perturbed, the rate of the ensuing H+ flux across the plasma membrane is determined by the H+ electrochemical gradient: its dependence on external K+ concentration indicates probable dependence on membrane potential and the rate depends on the H+ concentration gradient across the membrane. The large permeability at the 2-cell stage is absent or greatly diminished in the trophectoderm of blastocysts, but still present in the inner cell mass. Thus, the permeability to H+ appears to be developmentally regulated.

Metabolic co-operation between embryonic and embryonal carcinoma cells of the mouse

Development ◽  
1979 ◽  
Vol 54 (1) ◽  
pp. 263-275
Author(s):  
Stephen J. Gaunt ◽  
Virginia E. Papaioannou
Keyword(s):  
Embryonal Carcinoma ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Cells ◽  
Cone Cells ◽  
Ec Cells ◽  
Hypoxanthine Guanine Phosphoribosyltransferase ◽  
Early Mouse ◽  
Intercellular Exchange ◽  
Embryonic Ectoderm

Mouse embryonal carcinoma (EC) cells form permeable junctions at their homotypic cell-to-cell contacts which permit intercellular exchange of metabolites (metabolic co-operation). Hooper & Slack (1977) showed how this exchange could be detected by autoradiography as the transfer of [3H]nucleotides between PCI3 (a pluripotential EC line) and PCI 3- TG8 (a variant of PC13 which is deficient in hypoxanthine guanine phosphoribosyltransferase). We now show that cells taken from several different tissues of early mouse embryos, that is, from the morula, the inner cell mass of the blastocyst, and the endoderm, mesoderm and embryonic ectoderm of the 8th day egg cylinder, are able to serve as donors of [3H] ucleotides to PC13TG8. In contrast, trophectodermal cells of cultured blastocysts, and the trophectodermal derivatives in the 8th day egg cylinder, that is, extra-embryonic ectoderm and ectoplacental cone cells, showed little or no metabolic co-operation with PC13TG8. With reference to some common properties of EC and embryonic cells, we suggest how our findings may provide insight into cell-to-cell interactions in the early mouse embryo.

Features of cell lineage in preimplantation mouse development

Development ◽  
1978 ◽  
Vol 48 (1) ◽  
pp. 53-72
Author(s):  
C. F. Graham ◽  
Z. A. Deussen
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Lineage ◽  
The Other ◽  
Mouse Development ◽  
Cell Stage ◽  
Daughter Cells ◽  
Preimplantation Mouse ◽  
Peripheral Cells

The cell lineage of the mouse was studied from the 2-cell stage to the blastocyst. Lineage to the 8-cell stage was followed under the microscope. Each cell from the 2-cell stage divided to form two daughter cells which remained attached. Subsequently, these two daughters each produced two descendants; one of these descendants regularly lay deep in the structure of the embryo while the other was peripheral. Lineage to the blastocyst was followed by injecting oil drops into cells at the 8-cell stage, and then following the segregation of these drops into the inner cell mass and trophectoderm. Between the 8-cell stage and the blastocyst, the deep cells contributed more frequently to the inner cell mass than did the peripheral cells.

Expression of the gap junction proteins connexin31 and connexin43 correlates with communication compartments in extraembryonic tissues and in the gastrulating mouse embryo, respectively

1996 ◽  
Vol 109 (1) ◽  
pp. 191-197
Author(s):  
E. Dahl ◽  
E. Winterhager ◽  
B. Reuss ◽  
O. Traub ◽  
A. Butterweck ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Confocal Laser ◽  
Mouse Development ◽  
Confocal Laser Scan Microscopy ◽  
Early Mouse ◽  
Junction Proteins ◽  
In Cells ◽  
Extraembryonic Tissues

We have characterized the pattern of connexin expression in embryonic and extraembryonic tissues during early mouse development. In the preimplantation blastocyst, at 3.5 days post coitum (dpc), immunofluorescent signals specific for connexin31 and connexin43 proteins were present in both the inner cell mass and the trophectoderm, as shown by confocal laser scan microscopy. Immediately after implantation at 6.5 dpc, however, we find complete compartmentation of these two connexins: connexin31 mRNA and protein are expressed exclusively in cells derived from the trophectoderm lineage, whereas connexin43 mRNA and protein are detected in cells derived from the inner cell mass. This expression pattern of connexin31 and connexin43 is maintained at 7.5 dpc when the axial polarity of the mouse embryo is established. It correlates with the communication compartments in extraembryonic tissues and the gastrulating mouse embryo, respectively. The communication boundary between those compartments may be due to incompatibility of connexin31 and connexin43 hemichannels, which do not communicate with each other in cell culture.

scholarly journals Blastomeres arising from the first cleavage division have distinguishable fates in normal mouse development

Development ◽  
2001 ◽  
Vol 128 (19) ◽  
pp. 3739-3748 ◽  
Author(s):  
Karolina Piotrowska ◽  
Florence Wianny ◽  
Roger A. Pedersen ◽  
Magdalena Zernicka-Goetz
Keyword(s):  
Inner Cell Mass ◽  
Angular Displacement ◽  
Cell Mass ◽  
Boundary Region ◽  
Lineage Tracing ◽  
Mouse Development ◽  
Cleavage Division ◽  
Cell Stage ◽  
Early Embryos ◽  
Cell Mouse Embryo

Two independent studies have recently suggested similar models in which the embryonic and abembryonic parts of the mouse blastocyst become separated already by the first cleavage division. However, no lineage tracing studies carried out so far on early embryos provide the support for such a hypothesis. Thus, to re-examine the fate of blastomeres of the two-cell mouse embryo, we have undertaken lineage tracing studies using a non-perturbing method. We show that two-cell stage blastomeres have a strong tendency to develop into cells that comprise either the embryonic or the abembryonic parts of the blastocyst. Moreover, the two-cell stage blastomere that is first to divide will preferentially contribute its progeny to the embryonic part. Nevertheless, we find that the blastocyst embryonic-abembryonic axis is not perfectly orthogonal to the first cleavage plane, but often shows some angular displacement from it. Consequently, there is a boundary zone adjacent to the interior margin of the blastocoel that is populated by cells derived from both earlier and later dividing blastomeres. The majority of cells that inhabit this boundary region are, however, derived from the later dividing two-cell stage blastomere that contributes predominantly to the abembryonic part of the blastocyst. Thus, at the two-cell stage it is already possible to predict which cell will contribute a greater proportion of its progeny to the abembryonic part of the blastocyst (region including the blastocyst cavity) and which to the embryonic part (region containing the inner cell mass) that will give rise to the embryo proper.

scholarly journals A Nanog-dependent gene cluster initiates the specification of the pluripotent epiblast

2019 ◽  
Author(s):  
Nicolas Allègre ◽  
Sabine Chauveau ◽  
Cynthia Dennis ◽  
Yoan Renaud ◽  
Lorena Valverde Estrella ◽  
...  
Keyword(s):  
Inner Cell Mass ◽  
Es Cells ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Mammalian Embryo ◽  
Expression Variability ◽  
Heterogeneous Expression ◽  
Fgf Signalling ◽  
Early Mouse ◽  
Cell Expression

SummaryThe epiblast (Epi) is the source of embryonic stem (ES) cells and all embryonic tissues. It differentiates alongside the primitive endoderm (PrE) in a randomly distributed “salt and pepper” pattern from the inner cell mass (ICM) during preimplantation of the mammalian embryo. NANOG and GATA6 are key regulators of this binary differentiation event, which is further modulated by heterogeneous FGF signalling. When and how Epi and PrE lineage specification is initiated within the developing embryo is still unclear. Here we generated NANOG and GATA6 double KO (DKO) mouse embryos and performed single-cell expression analyses. We found that the ICM was unable to differentiate in the DKO mice, allowing us to characterize the ICM precursor state. The normally heterogeneous expression of Fgf4 between cells was significantly reduced in DKO ICMs, impairing FGF signalling. In contrast, several pluripotency markers did still display cell-to-cell expression variability in DKO ICMs. This revealed a primary heterogeneity independent of NANOG, GATA6 and FGF signalling that may also be conserved in humans. We found that NANOG is key in the initiation of epiblast specification already between the 16- and 32-cell stages, enabling the cell-clustered expression of many pluripotency genes. Our data uncover previously unknown biology in the early mouse embryo with potential implications for the field of pluripotent stem cells in human and other mammals.

Two CDC25 homologues are differentially expressed during mouse development

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2047-2056 ◽  
Author(s):  
D. Wickramasinghe ◽  
S. Becker ◽  
M.K. Ernst ◽  
J.L. Resnick ◽  
J.M. Centanni ◽  
...  
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Developmental Expression ◽  
Preimplantation Embryos ◽  
Mouse Development ◽  
Cell Stage ◽  
Phosphatase Domain ◽  
Cell Cycles ◽  
Stage Of Development ◽  
Drosophila Homolog

The cdc25 gene product is a tyrosine phosphatase that acts as an initiator of M-phase in eukaryotic cell cycles by activating p34cdc2. Here we describe the cloning and characterization of the developmental expression pattern of two mouse cdc25 homologs. Sequence comparison of the mouse genes with human CDC25 genes reveal that they are most likely the mouse homologs of human CDC25A and CDC25B respectively. Mouse cdc25a, which has not been described previously, shares 84% sequence identity with human CDC25A and has a highly conserved phosphatase domain characteristic of all cdc25 genes. A glutathione-S-transferase-cdc25a fusion protein can hydrolyze para-nitro-phenylphosphate confirming that cdc25a is a phosphatase. In adult mice, cdc25a transcripts are expressed at high levels in the testis and at lower levels in the ovary, particularly in germ cells; a pattern similar to that of twn, a Drosophila homolog of cdc25. Lower levels of transcript are also observed in kidney, liver, heart and muscle, a transcription pattern that partially overlaps, but is distinct from that of cdc25b. Similarly, in the postimplantation embryo cdc25a transcripts are expressed in a pattern that differs from that of cdc25b. cdc25a expression is observed in most developing embryonic organs while cdc25b expression is more restricted. An extended analysis of cdc25a and cdc25b expression in preimplantation embryos has also been carried out. These studies reveal that cdc25b transcripts are expressed in the one-cell embryo, decline at the two-cell stage and are re-expressed at the four-cell stage, following the switch from maternal to zygotic transcription which mirrors the expression of string, another Drosophila homolog of cdc25. In comparison, cdc25a is not expressed in the preimplantation embryo until the late blastocyst stage of development, correlating with the establishment of a more typical G1 phase in the embryonic cell cycles. Both cdc25a and cdc25b transcripts are expressed at high levels in the inner cell mass and the trophectoderm, which proliferate rapidly prior to implantation. These data suggest the cdc25 genes may have distinct roles in regulating the pattern of cell division during mouse embryogensis and gametogenesis.

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