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.

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 Selective activation of FZD7 promotes mesendodermal differentiation of human pluripotent stem cells

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Diana Gumber ◽  
Myan Do ◽  
Neya Suresh Kumar ◽  
Pooja R Sonavane ◽  
Christina C N Wu ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Primitive Streak ◽  
The Other ◽  
Single Chain ◽  
Selective Activation ◽  
Mammalian Embryo ◽  
Surface Receptors ◽  
Wnt Proteins ◽  
Single Chain Variable Fragments ◽  
Selective Interactions

WNT proteins are secreted symmetry breaking signals that interact with cell surface receptors of the FZD family to regulate a multitude of developmental processes. Studying selectivity between WNTs and FZDs has been hampered by the paucity of purified WNT proteins and by their apparent non-selective interactions with the FZD receptors. Here, we describe an engineered protein, called F7L6, comprised of antibody-derived single-chain variable fragments, that selectively binds to human FZD7 and the co-receptor LRP6. F7L6 potently activates WNT/β-catenin signaling in a manner similar to Wnt3a. In contrast to Wnt3a, F7L6 engages only FZD7 and none of the other FZD proteins. Treatment of human pluripotent stem (hPS) cells with F7L6 initiates transcriptional programs similar to those observed during primitive streak formation and subsequent gastrulation in the mammalian embryo. This demonstrates that selective engagement and activation of FZD7 signaling is sufficient to promote mesendodermal differentiation of hPS cells.

scholarly journals Transcriptional Regulator BPTF/FAC1 Is Essential for Trophoblast Differentiation during Early Mouse Development

2008 ◽  
Vol 28 (22) ◽  
pp. 6819-6827 ◽  
Author(s):  
Tobias Goller ◽  
Franz Vauti ◽  
Suresh Ramasamy ◽  
Hans-Henning Arnold
Keyword(s):  
Subsequent Development ◽  
Transcriptional Regulator ◽  
Primitive Streak ◽  
Embryonic Lethality ◽  
Visceral Endoderm ◽  
Loss Of Function ◽  
Mouse Development ◽  
Trophoblast Stem Cells ◽  
Early Mouse ◽  
Ectoplacental Cone

ABSTRACT The putative transcriptional regulator BPTF/FAC1 is expressed in embryonic and extraembryonic tissues of the early mouse conceptus. The extraembryonic trophoblast lineage in mammals is essential to form the fetal part of the placenta and hence for the growth and viability of the embryo in utero. Here, we describe a loss-of-function allele of the BPTF/FAC1 gene that causes embryonic lethality in the mouse. BPTF/FAC1-deficient embryos form apparently normal blastocysts that implant and develop epiblast, visceral endoderm, and extraembryonic ectoderm including trophoblast stem cells. Subsequent development of mutants, however, is arrested at the early gastrula stage (embryonic day 6.5), and virtually all null embryos die before midgestation. Most notably, the ectoplacental cone is drastically reduced or absent in mutants, which may cause the embryonic lethality. Development of the mutant epiblast is also affected, as the anterior visceral endoderm and the primitive streak do not form correctly, while brachyury-expressing mesodermal cells arise but are delayed. The mutant phenotype suggests that gastrulation is initiated, but no complete anteroposterior axis of the epiblast appears. We conclude that BPTF/FAC1 is essential in the extraembryonic lineage for correct development of the ectoplacental cone and fetomaternal interactions. In addition, BPTF/FAC1 may also play a role either directly or indirectly in anterior-posterior patterning of the epiblast.

scholarly journals Selective activation of FZD7 promotes mesendodermal differentiation of human pluripotent stem cells.

2020 ◽  
Author(s):  
Diana Gumber ◽  
Myan Do ◽  
Neya Suresh Kumar ◽  
Christina C. N. Wu ◽  
Dennis Carson ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Primitive Streak ◽  
Beta Catenin ◽  
Single Chain ◽  
Selective Activation ◽  
Mammalian Embryo ◽  
Surface Receptors ◽  
Wnt Proteins ◽  
Single Chain Variable Fragments ◽  
Selective Interactions

WNT proteins are secreted symmetry breaking signals that interact with cell surface receptors of the FZD family to regulate a multitude of developmental processes. Studying selectivity between WNTs and FZDs has been hampered by the paucity of purified WNT proteins and by their apparent non-selective interactions with the FZD receptors. Here we describe an engineered protein, called F7L6, comprised of antibody-derived single chain variable fragments that selectively binds to human FZD7 and the co-receptor LRP6. F7L6 potently activates WNT/beta-catenin signaling in a manner similar to Wnt3a. In contrast to Wnt3a, F7L6 engages only FZD7 and none of the other FZD proteins. Treatment of human pluripotent stem (hPS) cells with F7L6 initiates transcriptional programs similar to those observed during primitive streak formation and subsequent gastrulation in the mammalian embryo. This demonstrates that selective engagement and activation of FZD7 signaling is sufficient to promote mesendodermal differentiation of hPS cells.

scholarly journals Identification in Xenopus of a structural homologue of the Drosophila gene snail

Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 967-973 ◽  
Author(s):  
M.G. Sargent ◽  
M.F. Bennett
Keyword(s):  
Transcription Factor ◽  
Zinc Fingers ◽  
Equatorial Zone ◽  
Zygotic Transcription ◽  
Mesoderm Formation ◽  
Calcium And Magnesium ◽  
Inducing Factors ◽  
Mesoderm Inducing Factors ◽  
Structural Homologue ◽  
Binding Loop

We have cloned a Xenopus cDNA that is related to snail, a gene that is required for mesoderm formation in Drosophila. The cDNA encodes a protein that contains five zinc-fingers that closely resemble those of snail. In the non-canonical parts of the DNA-binding loop, there is almost 90% homology between snail and xsna. The corresponding mRNA (xsna) is expressed strongly at the start of zygotic transcription simultaneously with the transcription factor EF1 alpha. In early gastrulae, xsna is equally distributed between the dorsal and ventral halves of the equatorial zone. The possibility that the capacity to synthesise xsna is more localised before the start of zygotic transcription has been investigated by culturing fragments of stage 8 embryos until xsna is synthesised. The capacity to synthesise xsna at stage 8 is located principally in the dorsal half of the equatorial zone. A small amount of maternal xsna is localised in the vegetal hemisphere before zygotic transcription starts. xsna is not present in isolated animal caps but can be induced by the mesoderm-inducing factors XTC-MIF and bFGF. Synthesis of xsna does not occur autonomously in dispersed cells but is restored when cells reaggregate in the presence of calcium and magnesium.

Ontogeny of hyaluronan secretion during early mouse development

Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 483-492 ◽  
Author(s):  
J.J. Brown ◽  
V.E. Papaioannou
Keyword(s):  
Primitive Streak ◽  
Synthetic Activity ◽  
Visceral Endoderm ◽  
Mouse Development ◽  
Cell Lineages ◽  
Early Mouse ◽  
Serum Substitute ◽  
Embryonic Ectoderm

The ontogeny of hyaluronan (HA) secretion during early mouse embryogenesis has been investigated using a biotin-labelled HA-binding complex from cartilage proteoglycan. HA is first secreted by visceral endoderm cells of the early egg cylinder on day 5.5 post coitum (p.c.), predominantly into the expanding yolk cavity. On day 6.5 p.c., HA is present in both the yolk and proamniotic cavities, but pericellular staining is restricted to the visceral endoderm and a population of embryonic ectoderm cells at the antimesometrial end of the proamniotic cavity. By the primitive streak stage, HA is secreted into the ectoplacental, exocoelomic, amniotic and yolk cavities, whilst the only cells exhibiting pericellular staining are those of the embryonic and extraembryonic mesoderm, including the allantois. Comparisons of HA-staining patterns of cultured whole blastocysts, microdissected trophectoderm fragments and immunosurgically isolated inner cell masses, revealed no trophoblast-associated HA secretion during outgrowth in vitro but significant synthetic activity by the endodermal derivatives of differentiating inner cell masses. To identify the cell lineages responsible for secretion of HA into the embryonic cavities and to investigate the origin of the HA observed around migrating mesoderm cells, day 7.5 p.c. primitive streak stage conceptuses were dissected into their various embryonic and extraembryonic cell lineages. HA secretion was observed after short-term suspension culture of mesoderm, embryonic ectoderm and embryonic endoderm, but was undetectable in fragments of ectoplacental cone, parietal yolk sac (primary giant trophoblast and parietal endoderm), extraembryonic ectoderm or extraembryonic endoderm. The level of synthesis by the HA-positive tissues was markedly enhanced by culture in medium containing serum, compared with that obtained following culture in medium supplemented with a defined serum substitute containing insulin, transferrin, selenous acid and linoleic acid. This suggests that additional growth factors, present in serum but absent from the serum substitute, are required for optimal HA synthesis by the HA-secreting tissues in vitro, and probably also in vivo. The implications of these events for implantation and the development of peri- and early post-implantation mouse embryos are discussed, and a new role for HA in the initial formation and expansion of the embryonic cavities is proposed.

scholarly journals Brachyury cooperates with Wnt/β-Catenin signalling to elicit Primitive Streak like behaviour in differentiating mouse ES cells.

2014 ◽  
Author(s):  
David Andrew Turner ◽  
Pau Rué ◽  
Jonathan P Mackenzie ◽  
Eleanor Davies ◽  
Alfonso Martinez Arias
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Es Cells ◽  
Single Cells ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Mouse Development ◽  
Mesenchymal Transition ◽  
Mouse Es Cells ◽  
Cellular Events ◽  
Early Mouse

The formation of the Primitive Streak is the first visible sign of gastrulation, the process by which the three germ layers are formed from a single epithelium during early development. Embryonic Stem Cells (ESCs) provide a good system to understand the molecular and cellular events associated with these processes. Previous work, both in embryos and in culture, has shown how converging signals from both Nodal/TGFβR and Wnt/β-Catenin signalling pathways specify cells to adopt a Primitive Streak like fate and direct them to undertake an epithelial to mesenchymal transition (EMT). However, many of these approaches have relied on genetic analyses without taking into account the temporal progression of events within single cells. In addition, it is still unclear as to what extent events in the embryo are able to be reproduced in culture. Here, we combine flow-cytometry and a quantitative live single-cell imaging approach to demonstrate how the controlled differentiation of mouse ESCs (mESCs) towards a Primitive Streak fate in culture results in cells displaying many of the characteristics observed during early mouse development including transient Brachyury expression, EMT and increased motility. We also find that the EMT initiates the process, and this is both fuelled and terminated by the action of Bra, whose expression is dependent on the EMT and β-Catenin activity. As a consequence of our analysis, we propose that a major output of Brachyury expression is in controlling the velocity of the cells that are transiting out of the Primitive Streak.

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