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At least 235 records · Page 13Linked to original sources
PubMed1994

Heparitinase inhibition of mesoderm induction and gastrulation in Xenopus laevis embryos.

We have examined the involvement of proteoglycan molecules in the induction of mesodermal tissue in Xenopus laevis embryos. Blastocoelic injections of the enzyme heparitinase at early blastula stages lead to gastrulation defects and to failures in the development of anterior embryonic structures. The period of sensitivity of embryos to this treatment suggests a possible role for these molecules during mesoderm induction. We show that heparan sulfate proteoglycans (HSPGs) and chondroitin sulfate proteoglycans are the predominant sulfated glycoconjugates synthesized in early Xenopus embryos and that HSPGs are degraded by blastocoelic injections of heparitinase. Further, bFGF induction of mesoderm in explants of Xenopus stage 8 embryonic animal cap tissue is blocked by heparitinase but not by Chondroitinase ABC, using three separate criteria of mesoderm induction. Since HSPGs present in blastula animal cap cells are digested by heparitinase under the culture conditions used in the mesoderm-induction assay, we suggest that cell-surface heparan sulfate proteoglycans are required for basic fibroblast growth factor-mediated mesoderm induction.

Activins↗
PubMed1996

The fate diversity of mesodermal cells within the heart field during chicken early embryogenesis.

In gastrulation stage embryos of birds and mammals, the heart field is established as mesodermal crescents flanking the area rostrolateral to Hensen's node. Subsequent fusion of the bilateral heart primordia gives rise to a single tubular heart consisting of two epithelial layers: an outer myocardium and an inner endocardium. To date, it is uncertain whether these two distinct cell types of the heart arise from common or separate progenitor populations of mesodermal cells within the heart field. By retroviral single cell marking and tracking, we examined the diversity of cell populations present in the heart field of stage 4 chicken embryos. Here we demonstrate that individual mesodermal cells in the heart field gave rise to a clone consisting only of one cell type, either endocardial or myocardial cells; i.e., 95.1% of the mesoderm-derived clones were localized in the myocardium, while 4.9% of them were found in endocardium. No clones containing both of these two cell types were detected. The results suggest that the heart field mesoderm at stage 4 consists of at least two distinct subpopulations, containing more premyocardial cells than preendocardial cells. If there exists a common precursor of both myocardial and endocardial cells, the lineage diversification must occur at or prior to the arrival of mesodermal cells to the heart field.

Animals↗
PubMed1998

Paraxial-fated mesoderm is required for neural crest induction in Xenopus embryos.

Neural crest induction is thought to occur by a two-step process. Axially fated mesoderm induces neural plate, which is then recruited to neural crest by nonneural epidermal ectoderm at the neural plate border. This model suggests a rather indirect role for mesoderm in inducing neural crest. We extensively examined the role of mesoderm in neural crest induction by determining which types of mesoderm induce neural crest cells in Xenopus embryos. We found that noggin-dorsalized ventral marginal zone (VMZ) explants differentiate as melanocytes in the absence of axial mesoderm. Dorsalized VMZ is also a potent inducer of melanocytes when juxtaposed to animal cap ectoderm in recombinant explants. Dorsalized VMZ is analogous to the dorsal-lateral marginal zone (DLMZ) region of the embryo. Neural crest-inducing activities of gastrula stage DLMZ and dorsal marginal zone (DMZ) were also compared in recombinant explants. DLMZ was a stronger inducer of neural crest than was DMZ; DLMZ induced high levels of XSlug expression and melanocyte formation in recombinants, whereas DMZ weakly induced neural crest. In whole embryos lacking DLMZ, XSlug expression and melanocyte formation were significantly reduced; in contrast, no significant reduction of XSlug expression or melanocyte formation was seen in embryos lacking a DMZ. These results suggest that paraxial-fated mesoderm plays a central role in neural crest formation by inducing a novel type of lateral neural plate. This lateral neural plate is then recruited to neural crest by adjacent nonneural epidermal ectoderm.

Animals↗
PubMed1998

Smad7 inhibits mesoderm formation and promotes neural cell fate in Xenopus embryos.

We report the isolation and characterization of a new inhibitory Smad in Xenopus, which we have designated as Xenopus Smad7. Smad7 is present at fairly constant levels throughout early development and at blastula stages enriched in the ventral side of the animal hemisphere. The induction of mesoderm by TGF-beta-like signals is mediated by receptor ALK-4 and we show that Smad7 blocks signaling of ALK-4 in a graded fashion: lower levels of Smad7 block activation of dorsal mesoderm genes and higher levels block all mesoderm genes expression. Smad7 is able to directly activate neural markers in explants in the absence of mesoderm or endoderm. This neural-inducing activity of Smad7 may be due to inhibition of BMP-4 signaling because Smad7 can also block BMP-4-mediated mesoderm induction. Thus, Smad7 acts as a potent inhibitor of mesoderm formation and also activates the default neural induction pathway.

Activin Receptors, Type I↗
PubMed2001

Molecular integration of inductive and mesoderm-intrinsic inputs governs even-skipped enhancer activity in a subset of pericardial and dorsal muscle progenitors.

Individual somatic muscles and heart progenitors are specified at defined positions within the mesodermal layer of Drosophila. The expression of the homeobox gene even-skipped (eve) identifies one specific subset of cells in the dorsal mesoderm, which give rise to particular pericardial cells and dorsal body wall muscles. Genetic analysis has shown that the induction of eve in these cells involves the combined activities of genes encoding mesoderm-intrinsic factors, such as Tinman (Tin), and spatially restricted signaling activities that are largely derived from the ectoderm, particularly those encoded by wingless (wg) and decapentaplegic (dpp). Here we show that a Dpp-activated Smad protein, phosphorylated Mad, is colocalized in eve-expressing cells during an extended developmental period. We demonstrate further that a mesodermally active enhancer of eve contains several Smad and Tin binding sites that are essential for enhancer activity in vivo. This enhancer also contains a number of binding sites for the Wg-effector Pangolin (Pan/Lef-1), which are required for full levels of enhancer activity. However, we find that their main function is to prevent ectopic enhancer activity in the dorsal mesoderm. This suggests that, in the absence of Wg signaling, Pan binding serves to abrogate the synergistic activities of Smads and Tin in eve activation while, in cells that receive Wg signals, Pan is converted into a coactivator that promotes eve induction. Together, these data show that the eve enhancer integrates several regulatory pathways via the combinatorial binding of the mesoderm-intrinsic regulator Tin and the effectors of the Dpp and Wg signals.

Animals↗
PubMed1995

Insulin and insulin-like growth factor I prevent the mitogenic response of chick limb bud mesoderm cells to platelet-derived growth factor-AA.

Platelet-derived growth factor AA (PDGF-AA) increases DNA synthesis by chicken limb bud mesoderm in culture. Preincubation of either mesoderm from whole limb buds (stage 24-25) or mesoderm from the distal tip of the bud (stage 25) in insulin or insulin-like growth factor type I (IGF-I) resulted in increased DNA synthesis compared to control levels in two different types of medium. However, no further increase in DNA synthesis was then induced by PDGF-AA. This was found even when the level of DNA synthesis in IGF-I or insulin-containing medium was below that seen in cells treated only with PDGF. The response to PDGF was not dependent on the presence of serum in the medium. Insulin and IGF-I inhibited expression of the PDGF alpha receptor in mesoderm from whole limb buds. However, this was detected at times after the increase in DNA synthesis in response to PDGF was normally seen. IGF-I did not inhibit expression of the PDGF alpha receptor in mesoderm from distal limb bud tips. Thus, IGF-I and insulin modify the response of limb bud mesoderm to PDGF. The effects of IGF-I and insulin on receptor expression may be dependent on the cell populations present but do not appear to account for modulation of the PDGF-induced mitogenic response.

Animals↗
PubMed1987

Inhibition of polyamine synthesis reduces the growth rate and delays the expression of differentiated phenotypes in primary cultures of embryonic mesoderm from chick.

Inhibition of polyamine synthesis in early chick embryos blocks their development at gastrulation. Analyses of arrested embryos show that mesodermal outgrowth and differentiation are drastically impaired. To study these effects in greater detail, we have used primary cultures of embryonic mesoderm from chick. The cultures were treated with alpha-difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, the first and rate-limiting enzyme in polyamine synthesis. In control culture medium, mesodermal cells retained their in ovo outgrowth behavior and differentiation pattern. Addition of 10 mM DFMO to the culture medium, however, retarded attachment and outgrowth, and reduced the rate of proliferation of the mesodermal cells. Furthermore, the expression of differentiated phenotypes, such as beating heart tissue, erythroid cells, and adipocyte-like cells, was delayed. Simultaneous addition of 100 microM putrescine prevented or reduced the effects of DFMO, showing that these were indeed caused by polyamine deficiency. In the DFMO-treated mesoderm, DNA synthesis was markedly suppressed by the first day. Similar effects on RNA and protein synthesis developed at a later time. Our data suggest that a reduction in the concentrations of the polyamines decreases the rate of mesodermal cell proliferation, and as a consequence delays the expression of differentiated phenotypes.

Animals↗
PubMed1998

Inhibition of mesoderm formation by follistatin.

Mesoderm induction requires interaction between cells of the animal and vegetal hemispheres of the embryo. Several molecules have been proposed as candidates for mesoderm-inducing signals, with activin a particularly strong candidate. However, it has not been possible to inhibit mesoderm formation in vivo by specifically blocking activin action. Follistatin is able to inhibit the action of activin but not that of the mature region of Vg1, a member of the transforming growth factor beta family. Follistatin therefore provides a useful tool for distinguishing between signalling by these two factors. We have overexpressed Xenopus follistatin mRNA and analysed the expression of several mesodermal markers. Our results show an inhibition of mesodermal formation by follistatin in a concentration-dependent manner, showing the requirement of activin for mesodermal induction.

Animals↗
PubMed1984

The formation of supernumerary structures after grafting anterior quail wing bud mesoderm of various ages into chick wing buds.

Wedges of anterior quail mesoderm grafted into posterior slits in the wing buds of chick embryo hosts result in the formation of rods and nodules of supernumerary cartilage in a high percentage of cases. Identifiable digits do not form unless the ectoderm is allowed to remain on the grafts. Control experiments have shown that wedges of anterior or posterior wing mesoderm placed into homologous locations of host wing buds produce few or no supernumerary skeletal structures. Anterior-to-posterior grafts of stage 17 mesoderm evoke a 71.4% incidence of supernumerary cartilage. This percentage increases to 100% with stage 22 donor mesoderm. The percentage of supernumerary structures formed declines markedly with donor mesoderm of stages 24-30. By stages 35-36, only 10% of the grafts result in the formation of supernumerary structures. The period of decline coincides with the onset of overt cytodifferentiation within the donor mesoderm.

Age Factors↗
PubMed1985

Changes in the pericellular matrix during differentiation of limb bud mesoderm.

Mesodermal cells in the developing chick embryo limb bud appear morphologically homogeneous until stage 21. At stage 22 the prechondrogenic and premyogenic areas begin to condense, culminating in the appearance of cartilage and muscle by stage 25-26. We have examined changes in the hyaluronate-dependent pericellular matrices elaborated by mesodermal cells of the limb bud from different developmental stages and the corresponding changes in production of cell surface-associated and secreted glycosaminoglycans. When placed in culture, most early mesodermal cells (stage 17 lateral plate and stage 19 limb bud) exhibited pericellular coats as visualized by the exclusion of particles. These coats were removed by treatment of the cultures with Streptomyces hyaluronidase. Cells from stage 20-21 limb buds (precondensation) had smaller coats, whereas cells derived from stage 22, 24, and 26 limb buds (condensed chondrogenic and myogenic regions) lacked coats. However, coats were reformed during subsequent cytodifferentiation of chondrocytes; chondrocytes from stage 28 and 30 limb buds, and more mature chondrocytes from stage 38 tibiae, had pericellular coats. Thus, cytodifferentiation of cartilage is accompanied by extensive intercellular matrix accumulation in vivo and reacquisition of pericellular coats in vitro. Although their structure was still dependent on hyaluronate, chondrocyte coats were associated with increased proteoglycan content compared to the coats of early mesodermal cells. The amount of incorporation of [3H]acetate into cell surface hyaluronate remained relatively constant from stages 17 to 38, whereas in the medium compartment, incorporation into hyaluronate was more than 4-fold greater by stage 17 and 19 mesodermal cells than by cells from stages between 20 and 38. However, there was a progressive increase in incorporation into cell surface and medium chondroitin sulfate throughout these developmental stages. Thus, at the time of cellular condensation in the limb bud in vivo, we have observed a reduction in size of hyaluronate-dependent pericellular coats and a dramatic change in the relative proportion of hyaluronate and chondroitin sulfate produced by the mesodermal cells in vitro.

Acetates↗
PubMed1994

Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo.

We report the isolation of a Xenopus BMP receptor that is expressed maternally in the appropriate location to play a role in mesoderm induction. This receptor binds both BMP-2 and BMP-4 with high affinity. A truncated form of this BMP receptor specifically blocks BMP-4 signaling. Expression of this truncated BMP receptor during embryogenesis converts ventral mesoderm to dorsal mesoderm. Contrary to the popularly held view that ventral is the ground state for all mesoderm, our results suggest that formation of ventral mesoderm requires an active signal and that, in the absence of this ventral signal, dorsal mesoderm is formed.

Activins↗
PubMed1992

Retinoic acid prevents accumulation of a mesoderm-specific mRNA in the amphibian embryo.

Our greatest progress in understanding mechanisms of germ layer specification in vertebrates has come from studies of mesoderm induction in amphibian embryos. A key early observation was that transcriptional activation of the muscle actin gene and accumulation of its mRNA can be used as molecular markers of mesoderm induction. Recent studies of putative amphibian morphogens have shown that exposure to all-trans retinoic acid (RA) can perturb both neural and mesodermal patterning in the Xenopus embryo, and that RA can, under certain conditions, induce the synthesis of mRNA for a gene whose product is able to influence the patterning of the embryo. To characterize further the mechanism of mesoderm induction, the effect of RA exposure on the transcriptional properties of the muscle actin gene has been investigated. Interestingly, prior exposure of embryos to RA appears to inhibit accumulation, rather than initial activation, of the mesoderm-specific muscle actin transcript. This effect is concentration-dependent and is not observed with the ubiquitously expressed genes for cytoskeletal actin and translation elongation factor 1 alpha, nor with a neural-specific beta-tubulin gene. Thus, the molecular mechanism of mesoderm induction may include, in addition to transcriptional activation of specific genes, processes involved in maintenance of mRNA accumulation for those gene products.

Actins↗
PubMed2006

Activated Notch1 alters differentiation of embryonic stem cells into mesodermal cell lineages at multiple stages of development.

Signals of Notch transmembrane receptors function to regulate a wide variety of developmental cell fates. Here we investigate the role of Notch signaling in the development of mesodermal cell types by expressing a tamoxifen-inducible, activated form of Notch1 in embryonic stem cells (ESC). For differentiation of ESC into first mesodermal progenitor cells and then endothelial, mural, cardiac muscle and hematopoietic cells, the OP9 stroma co-culture system was used. Timed activation of Notch signaling by the addition of tamoxifen at various stages during differentiation of ESC into mesodermal cell lineages results in profound alterations in the generation of all of these cells. Differentiation of ESC into Flk1(+) mesodermal cells is inhibited by activated Notch. When Notch signaling is activated in mesodermal cells, generation of cardiac muscle, endothelial and hematopoietic cells is inhibited, favoring the generation of mural cells. Activation of Notch signaling in hematopoietic cells reduces colony formation and maintenance of hematopoiesis. These data suggest that Notch signaling plays a regulatory role in mesodermal development, cardiomyogenesis, the balanced generation of endothelial versus mural cells of blood vessels and hematopoietic development.

Cell Differentiation↗
PubMed2004

Pattern and morphogenesis of presumptive superficial mesoderm in two closely related species, Xenopus laevis and Xenopus tropicalis.

The mesoderm, comprising the tissues that come to lie entirely in the deep layer, originates in both the superficial epithelial and the deep mesenchymal layers of the early amphibian embryo. Here, we characterize the mechanisms by which the superficial component of the presumptive mesoderm ingresses into the underlying deep mesenchymal layer in Xenopus tropicalis and extend our previous findings for Xenopus laevis. Fate mapping the superficial epithelium of pregastrula stage embryos demonstrates ingression of surface cells into both paraxial and axial mesoderm (including hypochord), in similar patterns and amounts in both species. Superficial presumptive notochord lies medially, flanked by presumptive hypochord and both overlie the deep region of the presumptive notochord. These tissues are flanked laterally by superficial presumptive somitic mesoderm, the anterior tip of which also appears to overlay the presumptive deep notochord. Time-lapse recordings show that presumptive somitic and notochordal cells move out of the roof of the gastrocoel and into the deep region during neurulation, whereas hypochordal cells ingress after neurulation. Scanning electron microscopy at the stage and position where ingression occurs suggests that superficial presumptive somitic cells in X. laevis ingress into the deep region as bottle cells whereas those in X. tropicalis ingress by "relamination" (e.g., [Dev. Biol. 174 (1996) 92]). In both species, the superficially derived presumptive somitic cells come to lie in the medial region of the presumptive somites during neurulation. By the early tailbud stages, these cells lie at the horizontal myoseptum of the somites. The morphogenic pathway of these cells strongly resembles that of the primary slow muscle pioneer cells of the zebrafish. We present a revised fate map of Xenopus, and we discuss the conservation of superficial mesoderm within amphibians and across the chordates and its implications for the role of this tissue in patterning the mesoderm.

Animals↗
PubMed2004

The forkhead genes, Foxc1 and Foxc2, regulate paraxial versus intermediate mesoderm cell fate.

During vertebrate embryogenesis, the newly formed mesoderm is allocated to the paraxial, intermediate, and lateral domains, each giving rise to different cell and tissue types. Here, we provide evidence that the forkhead genes, Foxc1 and Foxc2, play a role in the specification of mesoderm to paraxial versus intermediate fates. Mouse embryos lacking both Foxc1 and Foxc2 show expansion of intermediate mesoderm markers into the paraxial domain, lateralization of somite patterning, and ectopic and disorganized mesonephric tubules. In gain of function studies in the chick embryo, Foxc1 and Foxc2 negatively regulate intermediate mesoderm formation. By contrast, their misexpression in the prospective intermediate mesoderm appears to drive cells to acquire paraxial fate, as revealed by expression of the somite markers Pax7 and Paraxis. Taken together, the data indicate that Foxc1 and Foxc2 regulate the establishment of paraxial versus intermediate mesoderm cell fates in the vertebrate embryo.

Animals↗
PubMed2005

A bHLH transcription factor gene, Twist-like 1, is essential for the formation of mesodermal tissues of Ciona juveniles.

Ascidian larval mesenchyme cells, comprising about 900 cells, are derived from the A7.6, B8.5 and B7.7 blastomere pairs in the 110-cell embryo. Previous studies showed that the properties of mesenchyme cells are not uniform among the three lines in embryos of Ciona savignyi and Ciona intestinalis. After metamorphosis, the larval mesenchyme cells form the mesodermal tissues or organs of the adult body. In the present study, the developmental fates of A7.6-, B8.5- and B7.7-line mesenchyme cells were traced using DiI to determine the origins of juvenile mesodermal tissues of C. savignyi. It was demonstrated that each of the A7.6-, B8.5- and B7.7-line mesenchyme cells is distributed in different positions of the larval trunk, and then give rise to the different mesodermal tissues of juveniles. Twist-like 1 is a transcription factor gene essential for the specification of larval mesenchyme cells. Knockdown of this gene with specific morpholino antisense oligonucleotides affected not only the specification of larval mesenchyme cells, but also the formation of most of the mesodermal tissues of juveniles. The juvenile mesodermal tissues in the Twist-like 1-knockdown specimen were never compensated by the surrounding tissues. The present results therefore indicate that Twist-like 1 is required for the differentiation of most mesodermal precursors of adults.

Animals↗
PubMed2000

Conservation of sequence and expression of Xenopus and zebrafish dHAND during cardiac, branchial arch and lateral mesoderm development.

dHAND and eHAND are related basic helix-loop-helix transcription factors that are expressed in the cardiac mesoderm and in numerous neural crest-derived cell types in chick and mouse. To better understand the evolutionary development of overlapping expression and function of the HAND genes during embryogenesis, we cloned the zebrafish and Xenopus orthologues. Comparison of dHAND sequences in zebrafish, Xenopus, chick, mouse and human demonstrated conservation throughout the protein. Expression of dHAND in zebrafish was seen in the earliest precursors of all lateral mesoderm at early gastrulation stages. At neurula and later stages, dHAND expression was observed in lateral precardiac mesoderm, branchial arch neural crest derivatives and posterior lateral mesoderm. At looping heart stages, cardiac dHAND expression remained generalized with no apparent regionalization. Interestingly, no eHAND orthologue was found in zebrafish. In Xenopus, dHAND and eHAND were co-expressed in the cardiac mesoderm without the segmental restriction seen in mice. Xenopus dHAND and eHAND were also expressed bilaterally in the lateral mesoderm without any left-right asymmetry. Within the branchial arches, XdHAND was expressed in a broader domain than XeHAND, similar to their mouse counterparts. Together, these data demonstrate conservation of HAND structure and expression across species.

Amino Acid Sequence↗
PubMed2002

The beta 3 tubulin gene is a direct target of bagpipe and biniou in the visceral mesoderm of Drosophila.

Previous studies have identified the NK homeobox gene bagpipe and the FoxF fork head domain gene biniou as essential regulators of visceral mesoderm development in Drosophila. Here we present additional genetic and molecular information on the functions of these two genes during visceral mesoderm morphogenesis and differentiation. We show that both genes are required for the activation of beta 3Tub60D in the visceral mesoderm, which encodes beta 3 tubulin. We demonstrate that a 254 bp derivative of a previously defined visceral mesoderm-specific enhancer element, vm1, from beta 3Tub60D contains one specific in vitro binding site for Bagpipe and two such sites for Biniou. While the wild-type version of the 254 bp enhancer is able to drive significant levels of reporter gene expression within the entire trunk visceral mesoderm, mutation of either the Bagpipe or the Biniou binding sites within this element results in a severe decrease of enhancer activity. Moreover, mutation of all three binding sites for Bagpipe and Biniou, respectively, results in the complete loss of enhancer activity. Together, these observations suggest that Bagpipe and Biniou serve as direct, partially redundant, and tissue-specific activators of the terminal differentiation gene beta 3Tub60D in the visceral mesoderm.

Amino Acid Sequence↗