scholarly journals Parathyroid hormone-related peptide as an endogenous inducer of parietal endoderm differentiation.

1993 ◽  
Vol 120 (1) ◽  
pp. 235-243 ◽  
Author(s):  
A van de Stolpe ◽  
M Karperien ◽  
C W Löwik ◽  
H Jüppner ◽  
G V Segre ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Inner Cell Mass ◽  
Es Cells ◽  
Cell Mass ◽  
Early Mouse Embryo ◽  
Endoderm Differentiation ◽  
Parathyroid Hormone Related Peptide ◽  
Parietal Endoderm ◽  
Early Mouse ◽  
Pthrp Receptor

Parathyroid hormone related peptide (PTHrP), first identified in tumors from patients with the syndrome of "Humoral Hypercalcemia of Malignancy," can replace parathyroid hormone (PTH) in activating the PTH-receptor in responsive cells. Although PTHrP expression is widespread in various adult and fetal tissues, its normal biological function is as yet unknown. We have examined the possible role of PTHrP and the PTH/PTHrP-receptor in early mouse embryo development. Using F9 embryonal carcinoma (EC) cells and ES-5 embryonic stem (ES) cells as in vitro models, we demonstrate that during the differentiation of these cells towards primitive and parietal endoderm-like phenotypes, PTH/PTHrP-receptor mRNA is induced. This phenomenon is correlated with the appearance of functional adenylate cyclase coupled PTH/PTHrP-receptors. These receptors are the mouse homologues of the recently cloned rat bone and opossum kidney PTH/PTHrP-receptors. Addition of exogenous PTH or PTHrP to RA-treated EC or ES cells is an efficient replacement for dBcAMP in inducing full parietal endoderm differentiation. Endogenous PTHrP is detectable at very low levels in undifferentiated EC and ES cells, and is upregulated in their primitive and parietal endoderm-like derivatives as assessed by immunofluorescence. Using confocal laser scanning microscopy on preimplantation mouse embryos, PTHrP is detected from the late morula stage onwards in developing trophectoderm cells, but not in inner cell mass cells. In blastocyst stages PTHrP is in addition found in the first endoderm derivatives of the inner cell mass. Together these results indicate that the PTH/PTHrP-receptor signalling system serves as a para- or autocrine mechanism for parietal endoderm differentiation in the early mouse embryo, thus constituting the earliest hormone receptor system involved in embryogenesis defined to date.

scholarly journals TAF10 (TAFII30) Is Necessary for TFIID Stability and Early Embryogenesis in Mice

2003 ◽  
Vol 23 (12) ◽  
pp. 4307-4318 ◽  
Author(s):  
William S. Mohan ◽  
Elisabeth Scheer ◽  
Olivia Wendling ◽  
Daniel Metzger ◽  
Làszlò Tora
Keyword(s):  
Cell Cycle Progression ◽  
Physiological Function ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Blastocyst Stage ◽  
Cycle Progression ◽  
Early Mouse Embryo ◽  
Its Gene ◽  
Tata Box Binding Protein ◽  
Early Mouse

ABSTRACT TAF10 (formerly TAFII30), is a component of TFIID and the TATA box-binding protein (TBP)-free TAF-containing complexes (TFTC/PCAF/STAGA). To investigate the physiological function of TAF10, we disrupted its gene in mice by using a Cre recombinase/LoxP strategy. Interestingly, no TAF10−/− animals were born from intercrosses of TAF10+/− mice, indicating that TAF10 is required for embryogenesis. TAF10−/− embryos developed to the blastocyst stage, implanted, but died shortly after ca. 5.5 days postcoitus. Surprisingly, trophoblast cells from TAF10−/− blastocysts were viable, whereas inner cell mass cells failed to survive, highlighting that TAF10 is not generally required for transcription in all cells. TAF10-deficient cells express normal levels of TBP and TAFs other than TAF10 but contain only partially formed TFIID, are endocycle arrested, and have undetectable levels of transcription. Thus, our results demonstrate that TAF10 is required for TFIID stability, cell cycle progression, and transcription in the early mouse embryo.

scholarly journals ECM-integrin signalling instructs cellular position-sensing to pattern the early mouse embryo

Development ◽  
2021 ◽  
Author(s):  
Esther Jeong Yoon Kim ◽  
Lydia Sorokin ◽  
Takashi Hiiragi
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Embryonic Cells ◽  
Primitive Endoderm ◽  
Integrin Β1 ◽  
Early Mouse Embryo ◽  
Position Sensing ◽  
Early Mouse

Development entails patterned emergence of diverse cell types within the embryo. In mammals, cells positioned inside the embryo give rise to the inner cell mass (ICM) that eventually forms the embryo proper. Yet the molecular basis of how these cells recognise their ‘inside’ position to instruct their fate is unknown. Here we show that provision of extracellular matrix (ECM) to isolated embryonic cells induces ICM specification and alters subsequent spatial arrangement between epiblast (EPI) and primitive endoderm (PrE) cells that emerge within the ICM. Notably, this effect is dependent on integrin β1 activity and involves apical to basal conversion of cell polarity. We demonstrate that ECM-integrin activity is sufficient for ‘inside’ positional signalling and it is required for proper EPI/PrE patterning. Our findings thus highlight the significance of ECM-integrin adhesion in enabling position-sensing by cells to achieve tissue patterning.

Effect of nitric oxide on early mouse embryo: Comparison of blastulation rates and inner cell mass/trophectoderm ratio

2002 ◽  
Vol 78 ◽  
pp. S283
Author(s):  
Navid Esfandiari ◽  
Tommaso Falcone ◽  
Ashok Agarwal ◽  
Ramadan A Saleh ◽  
Marjan Attaran ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mouse Embryo ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Early Mouse Embryo ◽  
Early Mouse

scholarly journals Parathyroid hormone-related peptide (PTHrP) induces parietal endoderm formation exclusively via the Type I PTH/PTHrP receptor

1999 ◽  
Vol 81 (1-2) ◽  
pp. 151-161 ◽  
Author(s):  
Mark H.G Verheijen ◽  
Marcel Karperien ◽  
Ung-il Chung ◽  
Merel van Wijuen ◽  
Heleen Heystek ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Type I ◽  
Related Peptide ◽  
Parathyroid Hormone Related Peptide ◽  
Parietal Endoderm ◽  
Pthrp Receptor

scholarly journals ECM-integrin signalling instructs cellular position-sensing to pattern the early mouse embryo

2021 ◽  
Author(s):  
Esther J.Y. Kim ◽  
Lydia Sorokin ◽  
Takashi Hiiragi
Keyword(s):  
Cell Polarity ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Embryonic Cells ◽  
Primitive Endoderm ◽  
Early Mouse Embryo ◽  
Position Sensing ◽  
Early Mouse

Development entails patterned emergence of diverse cell types within the embryo. In mammals, cells positioned inside the embryo gives rise to the inner cell mass (ICM) that eventually forms the embryo proper. Yet the molecular basis of how these cells recognise their inside position to instruct their fate is unknown. Here we show that cells perceive their position through extracellular matrix (ECM) and integrin-mediated adhesion. Provision of ECM to isolated embryonic cells induces ICM specification and alters subsequent spatial arrangement between epiblast (EPI) and primitive endoderm (PrE) cells that emerge within the ICM. Notably, this effect is dependent on integrin β 1 activity and involves apical to basal conversion of cell polarity. We demonstrate that ECM-integrin activity is sufficient for inside positional signalling and it is required for proper sorting of EPI/PrE cells. Our findings thus highlight the significance of ECM-integrin adhesion in enabling position-sensing by cells to achieve tissue patterning.

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.

scholarly journals Lineage allocation and asymmetries in the early mouse embryo

2003 ◽  
Vol 358 (1436) ◽  
pp. 1341-1349 ◽  
Author(s):  
Janet Rossant ◽  
Claire Chazaud ◽  
Yojiro Yamanaka
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Dependent Manner ◽  
Directional Growth ◽  
Early Mouse Embryo ◽  
Distinct Cell ◽  
And Migration ◽  
Set Up ◽  
Early Mouse ◽  
Anterior Posterior

The mouse blastocyst, at the time of implantation, has three distinct cell lineages: epiblast (EPI), trophoblast and primitive endoderm (PE). Interactions between these three lineages and their directional growth and migration are critical for establishing the initial asymmetries that result in anterior–posterior patterning of the embryo proper. We have re–investigated the timing of specification of the three lineages in relation to the differential allocation of progeny of the first two blastomeres to the embryonic versus abembryonic axis of the blastocyst. We find that the majority of cells of the inner cell mass (ICM) are specified to be EPI or PE by the mid 3.5 day blastocyst and that this is associated with localized expression of GATA–6 in the ICM. We propose a model for molecular specification of the blastocyst lineages in which a combination of cell division order, signal transduction differences between inner and outer cells and segregation of key transcription factors can produce a blastocyst in which all three lineages are normally set up in an ordered, lineage–dependent manner, but which can also reconstruct a blastocyst when division order or cell interactions are disturbed.

Cooperative interactions between extracellular matrix, integrins and parathyroid hormone-related peptide regulate parietal endoderm differentiation in mouse embryos

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4137-4148 ◽  
Author(s):  
O. Behrendtsen ◽  
C.M. Alexander ◽  
Z. Werb
Keyword(s):  
Extracellular Matrix ◽  
Parathyroid Hormone ◽  
Mouse Embryos ◽  
Collagen Type Iv ◽  
Related Peptide ◽  
Parathyroid Hormone Related Peptide ◽  
Parietal Endoderm ◽  
Alpha V Beta 3 ◽  
Endodermal Cells

The outgrowth of parietal endoderm (PE) cells from precursor endodermal cells is one of the first differentiation events that occur in mouse embryos. We have analyzed the molecular determinants of this process by placing isolated inner cell masses (ICMs) on defined extracellular matrix substrata in microdrop cultures. Differentiation and outgrowth of PE required a fibronectin substratum. Laminin supported the adhesion and outgrowth of visceral endoderm (VE) and actively suppressed the differentiation of PE in mixtures of fibronectin and laminin. Collagen type IV, gelatin, vitronectin or entactin supported little or no endodermal outgrowth. Trophectoderm (TE) cells have been implied to be important in PE induction in vivo. We found that recombination of ICMs in culture with TE cells, or with medium conditioned by TE cells, greatly increased the differentiation of PE. TE cells stimulated PE outgrowth on substrata other than fibronectin. One cytokine secreted by trophoblast and endodermal cells, parathyroid hormone-related peptide (PTHrP), was critical for outgrowth on any substratum. A function-perturbing antibody to PTHrP reduced the number of PE cells, whereas the addition of PTHrP increased that number. Furthermore, addition of PTHrP changed the substratum requirements for outgrowth, making laminin, vitronectin and low concentrations of fibronectin permissive for PE outgrowth. Immunostaining with anti-integrin antibodies showed that fully differentiated PE cells outgrowing on fibronectin expressed alpha 5, alpha 6 and alpha v beta 3 integrins. However, analysis of outgrowths in the presence of function-perturbing antibodies to alpha 5, alpha 6 and alpha v beta 3 integrins showed that these integrins directed PE outgrowth only on fibronectin, laminin and vitronectin substrata, respectively. We have shown that there is a cooperative interplay of extracellular matrix, integrins and PTHrP that modulates PE outgrowth.

The responsiveness of embryonic stem cells to alpha and beta interferons provides the basis of an inducible expression system for analysis of developmental control genes

1993 ◽  
Vol 13 (12) ◽  
pp. 7971-7976
Author(s):  
L M Whyatt ◽  
A Düwel ◽  
A G Smith ◽  
P D Rathjen
Keyword(s):  
Gene Expression ◽  
Inner Cell Mass ◽  
Es Cells ◽  
Expression System ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Expression Vectors ◽  
Developmental Control ◽  
Developmental Potential

Embryonic stem (ES) cells, derived from the inner cell mass of the preimplantation mouse embryo, are used increasingly as an experimental tool for the investigation of early mammalian development. The differentiation of these cells in vitro can be used as an assay for factors that regulate early developmental decisions in the embryo, while the effects of altered gene expression during early embryogenesis can be analyzed in chimeric mice generated from modified ES cells. The experimental versatility of ES cells would be significantly increased by the development of systems which allow precise control of heterologous gene expression. In this paper, we report that ES cells are responsive to alpha and beta interferons (IFNs). This property has been exploited for the development of inducible ES cell expression vectors, using the promoter of the human IFN-inducible gene, 6-16. The properties of these vectors have been analyzed in both transiently and stably transfected ES cells. Expression was minimal or absent in unstimulated ES cells, could be stimulated up to 100-fold by treatment of the cells with IFN, and increased in linear fashion with increasing levels of IFN. High levels of induced expression were maintained for extended periods of time in the continuous presence of the inducing signal or following a 12-h pulse with IFN. Treatment of ES cells with IFN did not affect their growth or differentiation in vitro or compromise their developmental potential. This combination of features makes the 6-16-based expression vectors suitable for the functional analysis of developmental control control genes in ES cells.

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.

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