msd is required for mesoderm induction in mice

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1335-1346 ◽  
Author(s):  
B.C. Holdener ◽  
C. Faust ◽  
N.S. Rosenthal ◽  
T. Magnuson
Keyword(s):  
Es Cells ◽  
Regulation Of Gene Expression ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Mesoderm Induction ◽  
Temporal Regulation ◽  
Basic Body ◽  
Vertebrate Embryo ◽  
Mesoderm Formation ◽  
Embryonic Ectoderm

Mesoderm induction is fundamental for establishing the basic body plan of the vertebrate embryo and mutations are critical for dissecting this process. Mouse embryos lacking msd (mesoderm deficiency) do not produce mesoderm but have well-defined extraembryonic and thickened embryonic ectoderm. Distribution of transcripts indicate that temporal regulation of gene expression relevant to gastrulation has begun but primitive-streak formation and mesoderm induction are blocked. Both msd-deficient embryos and embryonic stem (ES) cells fail to form highly differentiated structures of mesoderm origin, but are capable of ectodermal differentiation. Thus, the effects of the msd mutation are restricted to mesoderm formation and could result from the inability to respond to an inducing signal.

Brachyury - a gene affecting mouse gastrulation and early organogenesis

Development ◽  
1992 ◽  
Vol 116 (Supplement) ◽  
pp. 157-165 ◽  
Author(s):  
R. S. P. Beddington ◽  
P. Rashbass ◽  
V. Wilson
Keyword(s):  
Es Cells ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Coat Colour ◽  
Es Cell ◽  
Wild Type ◽  
Mesoderm Cell ◽  
Rostrocaudal Axis

Mouse embryos that are homozygous for the Brachyury (T) deletion die at mid-gestation. They have prominent defects in the notochord, the allantois and the primitive streak. Expression of the T gene commences at the onset of gastrulation and is restricted to the primitive streak, mesoderm emerging from the streak, the head process and the notochord. Genetic evidence has suggested that there may be an increasing demand for T gene function along the rostrocaudal axis. Experiments reported here indicate that this may not be the case. Instead, the gradient in severity of the T defect may be caused by defective mesoderm cell movements, which result in a progressive accumulation of mesoderm cells near the primitive streak. Embryonic stem (ES) cells which are homozygous for the T deletion have been isolated and their differentiation in vitro and in vivo compared with that of heterozygous and wild-type ES cell lines. In +/+ ↔ T/T ES cell chimeras the Brachyury phenotype is not rescued by the presence of wild-type cells and high level chimeras show most of the features characteristic of intact T/T mutants. A few offspring from blastocysts injected with T/T ES cells have been born, several of which had greatly reduced or abnormal tails. However, little or no ES cell contribution was detectable in these animals, either as coat colour pigmentation or by isozyme analysis. Inspection of potential +/+ ↔ T/T ES cell chimeras on the 11th or 12th day of gestation, stages later than that at which intact T/T mutants die, revealed the presence of chimeras with caudal defects. These chimeras displayed a gradient of ES cell colonisation along the rostrocaudal axis with increased colonisation of caudal regions. In addition, the extent of chimerism in ectodermal tissues (which do not invaginate during gastrulation) tended to be higher than that in mesodermal tissues (which are derived from cells invaginating through the primitive streak). These results suggest that nascent mesoderm cells lacking the T gene are compromised in their ability to move away from the primitive streak. This indicates that one function of the T genemay be to regulate cell adhesion or cell motility properties in mesoderm cells. Wild-type cells in +/+ ↔ T/T chimeras appear to move normally to populate trunk and head mesoderm, suggesting that the reduced motility in T/T cells is a cell autonomous defect

Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels

Blood ◽  
2004 ◽  
Vol 103 (1) ◽  
pp. 100-109 ◽  
Author(s):  
Zhengyu Wang ◽  
Kenneth Cohen ◽  
Ying Shao ◽  
Pamela Mole ◽  
David Dombkowski ◽  
...  
Keyword(s):  
Es Cells ◽  
Embryonic Stem ◽  
Mesoderm Induction ◽  
Es Cell ◽  
Vascular Differentiation ◽  
Phenotypic Characteristics ◽  
Coordinated Development ◽  
Modifying Factors ◽  
Ephrin Receptors ◽  
Ephrin Receptor

Abstract Differentiation of pluripotent embryonic stem (ES) cells is associated with expression of fate-specifying gene products. Coordinated development, however, must involve modifying factors that enable differentiation and growth to adjust in response to local microenvironmental determinants. We report here that the ephrin receptor, EphB4, known to be spatially restricted in expression and critical for organized vessel formation, modifies the rate and magnitude of ES cells acquiring genotypic and phenotypic characteristics of mesodermal tissues. Hemangioblast, blood cell, cardiomyocyte, and vascular differentiation was impaired in EphB4–/– ES cells in conjunction with decreased expression of mesoderm-associated, but not neuroectoderm-associated, genes. Therefore, EphB4 modulates the response to mesoderm induction signals. These data add differentiation kinetics to the known effects of ephrin receptors on mammalian cell migration and adhesion. We propose that modifying sensitivity to differentiation cues is a further means for ephrin receptors to contribute to tissue patterning and organization.

The T gene is necessary for normal mesodermal morphogenetic cell movements during gastrulation

Development ◽  
1995 ◽  
Vol 121 (3) ◽  
pp. 877-886 ◽  
Author(s):  
V. Wilson ◽  
L. Manson ◽  
W.C. Skarnes ◽  
R.S. Beddington
Keyword(s):  
T Cells ◽  
Neural Tube ◽  
Es Cells ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Distal Portion ◽  
Adhesion Properties ◽  
Cell Clones ◽  
Posterior Neuropore ◽  
Pass Through

The T (Brachyury) deletion in mouse is responsible for defective primitive streak and notochord morphogenesis, leading to a failure of the axis to elongate properly posterior to the forelimb bud. T/T embryonic stem (ES) cells colonise wild-type embryos, but in chimeras at 10.5 days post coitum (dpc) onwards they are found predominantly in the distal tail, while trunk paraxial and lateral mesoderm are deficient in T/T cells (Wilson, V., Rashbass, P. and Beddington, R. S. P. (1992) Development 117, 1321–1331). To determine the origin of this abnormal tissue distribution, we have isolated T/T and control T/+ ES cell clones which express lacZ constitutively using a gene trap strategy. Visualisation of T/T cell distribution in chimeric embryos throughout gastrulation up to 10.5 dpc shows that a progressive buildup of T/T cells in the primitive streak during gastrulation leads to their incorporation into the tailbud. These observations make it likely that one role of the T gene product is to act during gastrulation to alter cell surface (probably adhesion) properties as cells pass through the primitive streak. As the chimeric tail elongates at 10.5 dpc, abnormal morphology in the most distal portion becomes apparent. Comparison of T expression in the developing tailbud with the sites of accumulation of T/T cells in chimeras shows that T/T cells collect in sites where T would normally be expressed. T expression becomes internalised in the tailbud following posterior neuropore closure while, in abnormal chimeric tails, T/T cells remain on the surface of the distal tail. We conclude that prevention of posterior neuropore closure by the wedge of T/T cells remaining in the primitive streak after gastrulation is one source of the abnormal tail phenotypes observed. Accumulation of T/T cells in the node and anterior streak during gastrulation results in the preferential incorporation of T/T cells into the ventral portion of the neural tube and axial mesoderm. The latter forms compact blocks which are often fused with the ventral neural tube, reminiscent of the notochordal defects seen in intact mutants. Such fusions may be attributed to cell-autonomous changes in cell adhesion, possibly related to those observed at earlier stages in the primitive streak.

scholarly journals Developmental regulation of yolk sac hematopoiesis by Krüppel-like factor 6

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1357-1365 ◽  
Author(s):  
Nobuyuki Matsumoto ◽  
Atsushi Kubo ◽  
Huixian Liu ◽  
Kuniharu Akita ◽  
Friedrich Laub ◽  
...  
Keyword(s):  
Developmental Regulation ◽  
Es Cells ◽  
Embryonic Stem ◽  
Early Embryo ◽  
Yolk Sac ◽  
Homozygous Mutation ◽  
Mesoderm Induction ◽  
Mrna Levels ◽  
Mouse Development

Krüppel-like factor 6 (KLF6) is a member of a growing family of transcription factors that share a common 3 C2H2 zinc finger DNA binding domain and have broad activity in regulating proliferation and development. We have previously established that Klf6 is expressed in neuronal tissue, hindgut, heart, lung, kidney, and limb buds during midgestation. To explore the potential role of Klf6 in mouse development, we analyzed Klf6-/- mice and found that the homozygous mutation is embryonic lethal by embryonic day (E) 12.5 and associated with markedly reduced hematopoiesis and poorly organized yolk sac vascularization. Additionally, mRNA levels of Scl and Gata1 were reduced by approximately 80% in Klf6-/- yolk sacs. To further analyze this phenotype, we generated Klf6-/- embryonic stem (ES) cells by homologous recombination, and compared their capacity to differentiate into the hematopoietic lineage with that of either Klf6+/- or Klf6+/+ ES cells. Consistent with the phenotype in the early embryo, Klf6-/- ES cells displayed significant hematopoietic defects following differentiation into EBs. Prolongation of epiblast-like cells and delays in mesoderm induction were also observed in the Klf6-/- EBs, associated with delayed expression of Brachyury, Klf1, and Gata1. Forced expression of KLF6 using a tet-inducible system enhanced the hematopoietic potential of wild-type EBs. Collectively, these findings implicate Klf6 in ES-cell differentiation and hematopoiesis.

Rat embryonic ectoderm as renal isograft

Development ◽  
1986 ◽  
Vol 94 (1) ◽  
pp. 1-27
Author(s):  
Anton Švajger ◽  
Božica Levak-Švajger ◽  
Nikola Škreb
Keyword(s):  
Developmental Stage ◽  
Cell Population ◽  
Primitive Streak ◽  
Experimental Results ◽  
Current Concept ◽  
Embryonic Cells ◽  
Initial Cell ◽  
Mesoderm Formation ◽  
Distinct Features ◽  
Embryonic Ectoderm

Experimental results obtained many years ago revealed that during gastrulation (with the primitive streak and the mesoderm formation as distinct features) the early rodent embryo undergoes essential changes in its response to extrinsic teratogens (Russell & Russell, 1954; Wilson, 1954; Škreb, 1961; Škreb & Bijelić, 1962; Škreb & Frank, 1963). It has also been shown that the ultrastructural, histochemical and biosynthetic features of the embryo are subject to substantial changes during this period (Solter, Damjanov & Škreb, 1970, 1973; Dziadek & Adamson, 1978; Bode & Dziadek, 1979; Wartiovaara, Leivo & Vaheri, 1979; Jackson et al. 1981; Franke et al. 1982a, b). This suggests a restriction of developmental capacities (i.e. the loss of the capacity of regulation) in groups of embryonic cells at this developmental stage. According to the current concept, the initial cell population from which this restriction starts, resides within the embryonic ectoderm of the pregastrulation or preprimitive streak embryo (primitive or primary ectoderm).

Activated Fps/Fes partially rescues the in vivo developmental potential of Flk1-deficient vascular progenitor cells

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 912-920 ◽  
Author(s):  
Jody J. Haigh ◽  
Masatsugu Ema ◽  
Katharina Haigh ◽  
Marina Gertsenstein ◽  
Peter Greer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Es Cells ◽  
Consensus Sequence ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Developmental Potential ◽  
Vascular Progenitor Cells ◽  
Endothelial Growth Factor

AbstractRelatively little is known about the modulators of the vascular endothelial growth factor A (VEGF-A)/Flk1 signaling cascade. To functionally characterize this pathway, VEGF-A stimulation of endothelial cells was performed. VEGF-A–mediated Flk1 activation resulted in increased translocation of the endogenous Fps/Fes cytoplasmic tyrosine kinase to the plasma membrane and increased tyrosine phosphorylation, suggesting a role for Fps/Fes in VEGF-A/Flk1 signaling events. Addition of a myristoylation consensus sequence to Fps/Fes resulted in VEGF-A–independent membrane localization of Fps/Fes in endothelial cells. Expression of the activated Fps/Fes protein in Flk1-deficient embryonic stem (ES) cells rescued their contribution to the developing vascular endothelium in vivo by using ES cell–derived chimeras. Activated Fps/Fes contributed to this rescue event by restoring the migratory potential to Flk1 null progenitors, which is required for movement of hemangioblasts from the primitive streak region into the yolk sac proper. Activated Fps/Fes in the presence of Flk1 increased the number of hemangioblast colonies in vitro and increased the number of mesodermal progenitors in vivo. These results suggest that Fps/Fes may act synergistically with Flk1 to modulate hemangioblast differentiation into the endothelium. We have also demonstrated that activated Fps/Fes causes hemangioma formation in vivo, independently of Flk1, as a result of increasing vascular progenitor density.

Dual role of the basic helix-loop-helix transcription factor scleraxis in mesoderm formation and chondrogenesis during mouse embryogenesis

Development ◽  
1999 ◽  
Vol 126 (19) ◽  
pp. 4317-4329 ◽  
Author(s):  
D. Brown ◽  
D. Wagner ◽  
X. Li ◽  
J.A. Richardson ◽  
E.N. Olson
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Axial Skeleton ◽  
Bhlh Transcription Factor ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Mesoderm Formation ◽  
Cell Layers

Scleraxis is a basic helix-loop-helix (bHLH) transcription factor shown previously to be expressed in developing chondrogenic cell lineages during embryogenesis. To investigate its function in embryonic development, we produced scleraxis-null mice by gene targeting. Homozygous mutant embryos developed normally until the early egg cylinder stage (embryonic day 6.0), when they became growth-arrested and failed to gastrulate. Consistent with this early embryonic phenotype, scleraxis was found to be expressed throughout the embryo at the time of gastrulation before becoming restricted to chondrogenic precursor cells at embryonic day 9.5. At the time of developmental arrest, scleraxis-null embryos consisted of ectodermal and primitive endodermal cell layers, but lacked a primitive streak or recognizable mesoderm. Analysis of molecular markers of the three embryonic germ layers confirmed that scleraxis mutant embryos were unable to form mesoderm. By generating chimeric embryos, using lacZ-marked scleraxis-null and wild-type embryonic stem cells, we examined the ability of mutant cells to contribute to regions of the embryo beyond the time of lethality of homozygous mutants. Scleraxis-null cells were specifically excluded from the sclerotomal compartment of somites, which gives rise to the axial skeleton, and from developing ribs, but were able to contribute to most other regions of the embryo, including mesoderm-derived tissues. These results reveal an essential early role for scleraxis in mesoderm formation, as well as a later role in formation of somite-derived chondrogenic lineages, and suggest that scleraxis target genes mediate these processes.

scholarly journals An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

2013 ◽  
Author(s):  
David A Turner ◽  
Jamie Trott ◽  
Penelope Hayward ◽  
Pau Rué ◽  
Alfonso Martinez Arias
Keyword(s):  
Cell Fate ◽  
Neural Development ◽  
Es Cells ◽  
Initial Period ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Wnt Signalling ◽  
Dependent Manner ◽  
Cell Fate Decisions ◽  
Mouse Es Cells

Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analysed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation, cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a ?race for fates? in which the neuroectodermal fate has an advantage.

scholarly journals Dissection of gene regulatory networks in embryonic stem cells by means of high-throughput sequencing

2009 ◽  
Vol 390 (11) ◽  
Author(s):  
Christian Beisel ◽  
Renato Paro
Keyword(s):  
Gene Expression ◽  
Next Generation Sequencing ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Regulation Of Gene Expression ◽  
Embryonic Stem ◽  
Next Generation ◽  
Cell Fate Decisions ◽  
A Genome ◽  
Generation Sequencing

Abstract Transcription factor regulation of gene expression and chromatin-controlled epigenetic memory systems are closely cooperating in establishing the pluripotent state of embryonic stem (ES) cells and maintaining cell fate decisions throughout development of an organism. A thorough understanding of the regulatory transcriptional circuitry that rules the underlying plastic yet heritable gene expression programs in ES cells is of great importance. With the advent of next-generation sequencing technologies facilitating the quantitative assessment of functional genomics assays it is now feasible to interrogate transcription networks at a genome-wide scale. Here, we discuss the application of next-generation sequencing in elucidating the molecular mechanisms underlying ES cell function.

A differential display strategy identifies Cryptic, a novel EGF-related gene expressed in the axial and lateral mesoderm during mouse gastrulation

Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 429-442 ◽  
Author(s):  
M.M. Shen ◽  
H. Wang ◽  
P. Leder
Keyword(s):  
Growth Factor ◽  
Differential Display ◽  
Sequence Similarity ◽  
Es Cells ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Lateral Plate ◽  
New Family ◽  
Lateral Mesoderm

We have developed a differential display screening approach to identify mesoderm-specific genes, relying upon the differentiation of embryonic stem (ES) cells in vitro. Using this strategy, we have isolated a novel murine gene that encodes a secreted molecule containing a variant epidermal growth factor-like (EGF) motif. We named this gene Cryptic, based on its predicted protein sequence similarity with Cripto, which encodes an EGF-related growth factor. Based on their strong sequence similarities, we propose that Cryptic, Cripto, and the Xenopus FRL-1 gene define a new family of growth factor-like molecules, which we name the ‘CFC’ (Cripto, Frl-1, and Cryptic) family. Analysis of Cryptic expression by in situ hybridization shows that it is expressed during gastrulation in two spatial domains that correspond to the axial and lateral mesoderm. In the first domain of expression, Cryptic expression is progressively localized to the anterior primitive streak, the head process, and the node and notochordal plate. In the second domain, Cryptic expression is initially concentrated in the lateral region of the egg cylinder, and is later found circumferentially in the intermediate and lateral plate mesoderm. Furthermore, Cryptic expression can also be detected at the early head-fold stage in the midline neuroectoderm, and consequently is an early marker for the prospective floor plate of the neural tube. Expression of Cryptic ceases at the end of gastrulation, and has not been observed in later embryonic stages or in adult tissues. Thus, Cryptic encodes a putative signaling molecule whose expression suggests potential roles in mesoderm and/or neural patterning during gastrulation.

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