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At least 973 records · Page 54Linked to original sources
PubMed1991

The nature of the mesoderm-inducing signal in Xenopus: a transfilter induction study.

A transfilter apparatus is described, which is suitable for neutralization experiments on embryonic induction, and it is used to investigate the sensitivity of the Xenopus mesoderm-inducing signal to various inhibitors. The vegetal (inducing) tissue is placed on one side of a membrane sandwich and the animal (responding) tissue on the other side. The sandwich consists of a nylon gauze in between two Nucleopore filters and enables inhibitors in the solution to have effective access to the gap between the tissues. Control experiments show a high proportion of positive inductions of a ventral character. Using this apparatus, it is shown that the protein follistatin, which effectively inhibits activin A and B in vitro, has little or no effect on the natural signal. Likewise, antibodies to basic fibroblast growth factor, which inhibit in vitro, do not inhibit the natural signal. The two inhibitors together have a slight effect. It is concluded that neither activin nor bFGF are major components of the signal emitted by the vegetal cells of the Xenopus blastula and transmitted across the liquid gap, although they might have some other role to play in the process. Two agents of lower specificity do inhibit the transfilter induction: heparin and suramin. Suramin will also inhibit induction in animal-vegetal combinations with no intervening membranes while heparin does not. This suggests that the heparin inhibition can only occur when there is a liquid gap between the tissues, presumably because it can neutralize the signal in solution but cannot penetrate the explants themselves. The endogenous mesoderm-inducing factor(s) should therefore be sensitive to heparin in vitro.

Animals↗
PubMed1992

Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification.

We have cloned and sequenced a new member of the fibroblast growth factor family from Xenopus laevis embryo cDNA. It is most closely related to both mammalian kFGF (FGF-4) and FGF-6 but as it is not clear whether it is a true homologue of either of these genes we provisionally refer to it as XeFGF (Xenopus embryonic FGF). Two sequences were obtained, differing by 11% in derived amino acid sequence, which probably represent pseudotetraploid variants. Both the sequence and the behaviour of in vitro translated protein indicates that, unlike bFGF (FGF-2), XeFGF is a secreted molecule. Recombinant XeFGF protein has mesoderm-inducing activity with a specific activity similar to bFGF. XeFGF mRNA is expressed maternally and zygotically with a peak during the gastrula stage. Both probe protection and in situ hybridization showed that the zygotic expression is concentrated in the posterior of the body axis and later in the tailbud. Later domains of expression were found near the midbrain/hindbrain boundary and at low levels in the myotomes. Because of its biological properties and expression pattern, XeFGF is a good candidate for an inducing factor with possible roles both in mesoderm induction at the blastula stage and in the formation of the anteroposterior axis at the gastrula stage.

Amino Acid Sequence↗
PubMed1992

Developmental expression of the Xenopus int-2 (FGF-3) gene: activation by mesodermal and neural induction.

We have used a probe specific for the Xenopus homologue of the mammalian proto-oncogene int-2 (FGF-3) to examine the temporal and spatial expression pattern of the gene during Xenopus development. int-2 is expressed from just before the onset of gastrulation through to prelarval stages. In the early gastrula, it is expressed around the blastopore lip. This is maintained in the posterior third of the prospective mesoderm and neuroectoderm in the neurula. A second expression domain in the anterior third of the neuroectoderm alone appears in the late gastrula, which later resolves into the optic vesicles, hypothalamus and midbrain-hindbrain junction region. Further domains of expression arise in tailbud to prelarval embryos, including the stomodeal mesenchyme, the endoderm of the pharyngeal pouches and the cranial ganglia flanking the otocyst. It is shown, by treatment of blastula ectoderm with bFGF and activin, that int-2 can be expressed in response to mesoderm induction. By heterotypic grafting of gastrula ectoderm into axolotl neural plate, we have also demonstrated that int-2 can be expressed in response to neural induction. These results suggest that int-2 has multiple functions in development, including an early role in patterning of the anteroposterior body axis and a later role in the development of the tail, brain-derived structures and other epithelia.

Amino Acid Sequence↗
PubMed1993

Cross regulation of decapentaplegic and Ultrabithorax transcription in the embryonic visceral mesoderm of Drosophila.

The Drosophila decapentaplegic gene (dpp) encodes a TGF-beta family member involved in signal transduction during embryonic midgut formation. The shortvein (shv) class of cis-regulatory dpp mutants disrupt expression in parasegments 4 and 7 (ps4 and ps7) of the embryonic visceral mesoderm (VM) surrounding the gut and cause abnormalities in gut morphogenesis. We demonstrate that cis-regulatory elements directing expression in ps4 and ps7 are separable and identify DNA fragments that generate ps4 and ps7 expression patterns using reporter gene constructs. dpp reporter gene expression in both ps4 and ps7 is autoregulated as it requires endogenous dpp+ activity. Reporter gene ps7 expression requires the wild-type action of Ultra-bithorax (Ubx), and abdominal-A. Furthermore, the expression of certain Ubx reporter genes is coincident with dpp in the VM. Both the mis-expression of Ubx reporter genes in the developing gastric caecae at ps4 and its normal expression in ps7 are dependent upon endogenous dpp+ activity. We conclude that dpp both responds to and regulates Ubx in ps7 of the visceral mesoderm and that Ubx autoregulation within this tissue may be indirect as it requires more components than have previously been thought.

Animals↗
PubMed1993

The murine cripto gene: expression during mesoderm induction and early heart morphogenesis.

The murine cripto gene encodes a 171-aminoacid epidermal growth factor-related protein, with 93% similarity to its human counterpart in the 'EGF-like' domain. The murine cripto mRNA contains two B1 repeats in its 3' non-coding region and a 163-nucleotide homology to the human mRNA. The mouse cripto gene is expressed at low level in specific organs of the adult animal such as spleen, heart, lung and brain. In situ hybridization analysis during murine embryogenesis (day 6.2 to day 10.5) reveals a very restricted expression pattern. cripto transcripts are first detected in a few epiblastic cells at day 6.5. During gastrulation, the transcripts are expressed in the forming mesoderm and later during development cripto gene expression is restricted to the truncus arteriosus of the developing heart. This expression pattern suggests a role for cripto gene in the determination of the epiblastic cells that subsequently give rise to the mesoderm.

Amino Acid Sequence↗
PubMed1993

Embryonic mesodermal defects in alpha 5 integrin-deficient mice.

A loss of function mutation of the murine alpha 5 integrin gene generated by gene targeting in embryonic stem cells is a recessive embryonic lethal. The mutant embryos start to show observable defects by day 9 of gestation and die around day 10-11. The alpha 5-null embryos have pronounced defects in posterior trunk and yolk sac mesodermal structures, suggesting a role for alpha 5 beta 1 integrin in mesoderm formation, movement or function. However, the embryos progress significantly further than embryos null for fibronectin, for which alpha 5 beta 1 integrin is a receptor, suggesting the involvement of other fibronectin receptors. In vitro studies on cells derived from the alpha 5-null embryos confirm that the alpha 5 beta 1 integrin is not expressed on mutant cells and show that the mutant cells are able to assemble fibronectin matrix, form focal contacts, and migrate on fibronectin despite the complete absence of the alpha 5 beta 1 fibronectin receptor integrin. All these functions have previously been thought to involve or require alpha 5 beta 1. The results presented show that these cellular functions involving fibronectin can proceed using other receptors.

Animals↗
PubMed1994

Positive and negative signals from mesoderm regulate the expression of mouse Otx2 in ectoderm explants.

Otx2, a mouse homolog of the Drosophila orthodenticle gene, is first widely expressed in the epiblast but becomes progressively restricted to the anterior third of the embryo by the headfold stage. This progressive restriction correlates with the anterior migration of mesoderm in the embryo, suggesting that interactions with mesoderm may be involved in setting up the anterior domain of Otx2 expression in vivo. Using explant-recombination assays, we have obtained evidence that a positive signal from anterior mesendoderm is required to stabilize expression of Otx2 in vivo, whereas a negative signal from the later-forming posterior mesendoderm represses Otx2 expression in the posterior part of the embryo. We have also found that exogenous retinoic acid can mimic the effect of this negative signal and reduces the anterior domain of Otx2 expression.

Animals↗
PubMed1994

Wingless can bring about a mesoderm-to-ectoderm induction in Drosophila embryos.

By means of nuclear transplantations, we make mosaics in which largely wingless- embryos contain patches of wingless+ cells. In these genetic mosaics, using a standard assay for wingless function (the maintenance of engrailed expression), we uncover an induction across germ layers: Wingless made in the mesoderm can sustain engrailed expression in the ectoderm. This result makes clear that Wingless is expressed in the mesoderm until at least one hour after gastrulation and may function in this germ layer in the wild type.

Animals↗
PubMed1994

Epithelium formation in the Drosophila midgut depends on the interaction of endoderm and mesoderm.

The reorganization of mesenchymal cells into an epithelial sheet is a widely used morphogenetic process in metazoans. An example of such a process is the formation of the Drosophila larval midgut epithelium that develops through a mesenchymal-epithelial transition from endodermal midgut precursors. We have studied this process in wild type and a number of mutants that show defects in midgut epithelium formation. Our results indicate that the visceral mesoderm serves as a basal substratum to which endodermal cells have to establish direct contact in order to form an epithelium. Furthermore, we have analyzed the midgut phenotype of embryos mutant for the gene shotgun, and the results suggest that shotgun directs adhesion between midgut epithelial cells, which is independent from the adhesion between endoderm and visceral mesoderm.

Animals↗
PubMed1994

Pax-3 expression in segmental mesoderm marks early stages in myogenic cell specification.

Specification of the myogenic lineage begins prior to gastrulation and culminates in the emergence of determined myogenic precursor cells from the somites. The myoD family (MDF) of transcriptional activators controls late step(s) in myogenic specification that are closely followed by terminal muscle differentiation. Genes expressed in myogenic specification at stages earlier than MDFs are unknown. The Pax-3 gene is expressed in all the cells of the caudal segmental plate, the early mesoderm compartment that contains the precursors of skeletal muscle. As somites form from the segmental plate and mature, Pax-3 expression is progressively modulated. Beginning at the time of segmentation, Pax-3 becomes repressed in the ventral half of the somite, leaving Pax-3 expression only in the dermomyotome. Subsequently, differential modulation of Pax-3 expression levels delineates the medial and lateral halves of the dermomyotome, which contain precursors of axial (back) muscle and limb muscle, respectively. Pax-3 expression is then repressed as dermomyotome-derived cells activate MDFs. Quail-chick chimera and ablation experiments confirmed that the migratory precursors of limb muscle continue to express Pax-3 during migration. Since limb muscle precursors do not activate MDFs until 2 days after they leave the somite, Pax-3 represents the first molecular marker for this migratory cell population. A null mutation of the mouse Pax-3 gene, Splotch, produces major disruptions in early limb muscle development (Franz, T., Kothary, R., Surani, M. A. H., Halata, Z. and Grim, M. (1993) Anat. Embryol. 187, 153-160; Goulding, M., Lumsden, A. and Paquette, A. (1994) Development 120, 957-971). We conclude, therefore, that Pax-3 gene expression in the paraxial mesoderm marks earlier stages in myogenic specification than MDFs and plays a crucial role in the specification and/or migration of limb myogenic precursors.

Animals↗
PubMed1995

DWnt-4, a novel Drosophila Wnt gene acts downstream of homeotic complex genes in the visceral mesoderm.

Wnt genes encode putative cell signalling proteins which play crucial roles during development. From a library of DNA fragments associated, in vivo, with Ultrabithorax proteins, we isolated a novel Drosophila Wnt gene, DWnt-4. Neither a paralog nor an ortholog of the gene exist in the current repertoire of full-length Wnt sequences. DWnt-4 maps close (30 kb) to wingless, suggesting that the two Wnt genes derive from a duplication that occurred early in evolution, since they are significantly diverged in sequence and structure. Developmental expression of DWnt-4 partially overlaps that of wingless. The gene is transcribed following a segment polarity-like pattern in the posterior-most cells of each parasegment of the ectoderm, and at two locations that correspond to parasegments 4 and 8 of the visceral mesoderm. The control of DWnt-4 expression in the visceral mesoderm involves a network of regulatory molecules that includes Ultrabithorax and other proteins from the homeotic complex (HOM-C), as well as the TGF-beta decapentaplegic gene product.

Animals↗
PubMed1995

Myogenesis in paraxial mesoderm: preferential induction by dorsal neural tube and by cells expressing Wnt-1.

Previous studies have demonstrated that the neural tube/notochord complex is required for skeletal muscle development within somites. In order to explore the localization of myogenic inducing signals within the neural tube, dorsal or ventral neural tube halves were cultured in contact with single somites or pieces of segmental plate mesoderm. Somites and segmental plates cultured with the dorsal half of the neural tube exhibited 70% and 85% myogenic response rates, as determined by immunostaining for myosin heavy chain. This response was slightly lower than the 100% response to whole neural tube/notochord, but was much greater than the 30% and 10% myogenic response to ventral neural tube with and without notochord. These results demonstrate that the dorsal neural tube emits a potent myogenic inducing signal which accounts for most of the inductive activity of whole neural tube/notochord. However, a role for ventral neural tube/notochord in somite myogenic induction was clearly evident from the larger number of myogenic cells induced when both dorsal neural tube and ventral neural tube/notochord were present. To address the role of a specific dorsal neural tube factor in somite myogenic induction, we tested the ability of Wnt-1-expressing fibroblasts to promote paraxial mesoderm myogenesis in vitro. We found that cells expressing Wnt-1 induced a small number of somite and segmental plate cells to undergo myogenesis. This finding is consistent with the localized dorsal neural tube inductive activity described above, but since the ventral neural tube/notochord also possesses myogenic inductive capacity yet does not express Wnt-1, additional inductive factors are likely involved.

Animals↗
PubMed1995

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

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.

Animals↗
PubMed1996

The Xvent-2 homeobox gene is part of the BMP-4 signalling pathway controlling [correction of controling] dorsoventral patterning of Xenopus mesoderm.

We describe a novel Xenopus homeobox gene, Xvent-2, which together with the previously identified homeobox gene Xvent-1, defines a novel class of homeobox genes. vent genes are related by sequence homology, expression pattern and gain-of-function phenotype. Evidence is presented for a role of Xvent-2 in the BMP-4 pathway involved in dorsoventral patterning of mesoderm. (1) Xvent-2 is expressed in regions that also express BMP-4. (2) Xvent-2 and BMP-4 interact in a positive feedback loop. (3) Xvent-2 ventralizes dorsal mesoderm in a dose-dependent manner resulting in phenoytpes ranging from microcephaly to Bauchstück pieces, as does BMP-4. (4) Like BMP-4 and gsc, Xvent-2 and gsc are able to interact in a crossregulatory loop to suppress each other. (5) Microinjection of Xvent-2 mRNA can rescue dorsalization by a dominant-negative BMP-4 receptor. The results suggest that Xvent-2 functions in the BMP-4 signalling pathway that antagonizes the Spemann organizer.

Amino Acid Sequence↗
PubMed1997

Xmsx-1 modifies mesodermal tissue pattern along dorsoventral axis in Xenopus laevis embryo.

This study analyzes the expression and the function of Xenopus msx-1 (Xmsx-1) in embryos, in relation to the ventralizing activity of bone morphogenetic protein-4 (BMP-4). Expression of Xmsx-1 was increased in UV-treated ventralized embryos and decreased in LiCl-treated dorsalized embryos at the neurula stage (stage 14). Whole-mount in situ hybridization analysis showed that Xmsx-1 is expressed in marginal zone and animal pole areas, laterally and ventrally, but not dorsally, at mid-gastrula (stage 11) and late-gastrula (stage 13) stages. Injection of BMP-4 RNA, but not activin RNA, induced Xmsx-1 expression in the dorsal marginal zone at the early gastrula stage (stage 10+), and introduction of a dominant negative form of BMP-4 receptor RNA suppressed Xmsx-1 expression in animal cap and ventral marginal zone explants at stage 14. Thus, Xmsx-1 is a target gene specifically regulated by BMP-4 signaling. Embryos injected with Xmsx-1 RNA in dorsal blastomeres at the 4-cell stage exhibited a ventralized phenotype, with microcephaly and swollen abdomen. Histological observation and immunostaining revealed that these embryos had a large block of muscle tissue in the dorsal mesodermal area instead of notochord. On the basis of molecular marker analysis, however, the injection of Xmsx-1 RNA did not induce the expression of alpha-globin, nor reduce cardiac alpha-actin in dorsal marginal zone explants. Furthermore, a significant amount of alpha-actin was induced and alpha-globin was turned off in the ventral marginal zone explants injected with Xmsx-1. These results indicated that Xmsx-1 is a target gene of BMP-4 signaling, but possesses a distinct activity on dorsal-ventral patterning of mesodermal tissues.

Animals↗
PubMed1997

Direct neural induction and selective inhibition of mesoderm and epidermis inducers by Xnr3.

During gastrulation in amphibians, secreted factors from Spemann's organizer act on dorsal ectoderm to induce the central nervous system. A number of secreted factors produced by Spemann's organizer have recently been identified. The TGFbeta family member Xnr3 is similar in amino acid sequence to the mouse factor nodal and is expressed in a restricted group of cells in the superficial layer of Spemann's organizer. Xnr3, unlike the related factors nodal, Xnr1 and Xnr2, lacks mesoderm-inducing activity. We report here that Xnr3 can directly induce neural tissue in Xenopus ectoderm explants (animal caps). Injection of animal caps with either Xnr3 RNA or plasmids induces the expression of the pan-neural genes NCAM and nrp1, as well as the anterior neural marker Cpl1. A growing body of evidence suggests that neural induction in Xenopus proceeds as the default in the absence of epidermis inducers. The best candidates for the endogenous epidermis inducers are BMP-4 and BMP-7. The neural inducing activity of Xnr3 can be inhibited by overexpression of BMP-4, as has been observed with the neural inducers noggin, chordin and follistatin. Furthermore, Xnr3 can block mesoderm induction by BMP-4 and activin, but not by Xnr2. The structural basis underlying the divergent activities of Xnr2 and Xnr3 was analyzed using site-directed mutagenesis. Mutations introduced to the conserved cysteine residues characteristic of the TGFbeta family were found to inactivate Xnr2, but not Xnr3. The most unique feature of Xnr3 is the absence of a conserved cysteine at the C terminus of the protein. This feature distinguishes Xnr3 from other TGFbeta family members, including Xnr2. However, we observed that changing the C terminus of Xnr3 to more closely resemble other TGFbeta family members did not significantly alter its activity, suggesting that other structural features of Xnr3 distinguish its biological activity from Xnr2.

Amino Acid Sequence↗
PubMed1997

PDP1, a novel Drosophila PAR domain bZIP transcription factor expressed in developing mesoderm, endoderm and ectoderm, is a transcriptional regulator of somatic muscle genes.

In vertebrates, transcriptional control of skeletal muscle genes during differentiation is regulated by enhancers that direct the combinatorial binding and/or interaction of MEF2 and the bHLH MyoD family of myogenic factors. We have shown that Drosophila MEF2 plays a role similar to its vertebrate counterpart in the regulation of the Tropomyosin I gene in the development of Drosophila somatic muscles, however, unlike vertebrates, Drosophila MEF2 interacts with a muscle activator region that does not have binding sites for myogenic bHLH-like factors or any other known Drosophila transcription factors. We describe here the isolation and characterization of a component of the muscle activator region that we have named PDP1 (PAR domain protein 1). PDP1 is a novel transcription factor that is highly homologous to the PAR subfamily of mammalian bZIP transcription factors HLF, DBP and VBP/TEF. This is the first member of the PAR subfamily of bZIP transcription factors to be identified in Drosophila. We show that PDP1 is involved in regulating expression of the Tropomyosin I gene in somatic body-wall and pharyngeal muscles by binding to DNA sequences within the muscle activator that are required for activator function. Mutations that eliminate PDP1 binding eliminate muscle activator function and severely reduce expression of a muscle activator plus MEF2 mini-enhancer. These and previous results suggest that PDP1 may function as part of a larger protein/DNA complex that interacts with MEF2 to regulate transcription of Drosophila muscle genes. Furthermore, in addition to being expressed in the mesoderm that gives rise to the somatic muscles, PDP1 is also expressed in the mesodermal fat body, the developing midgut endoderm, the hindgut and Malpighian tubules, and the epidermis and central nervous system, suggesting that PDP1 is also involved in the terminal differentiation of these tissues.

Amino Acid Sequence↗
PubMed1998

The Tlx-2 homeobox gene is a downstream target of BMP signalling and is required for mouse mesoderm development.

TGFbeta-related factors are critical regulators of vertebrate mesoderm development. However, the signalling cascades required for their function during this developmental process are poorly defined. Tlx-2 is a homeobox gene expressed in the primitive streak of mouse embryos. Exogenous BMP-2 rapidly activates Tlx-2 expression in the epiblast of E6.5 embryos. A Tlx-2 promoter element responds to BMP-2 signals in P19 cells, and this response is mediated by BMP type I receptors and Smad1. These results suggest that Tlx-2 is a downstream target gene for BMP signalling in the primitive streak where BMP-4 and other TGFbeta-related factors are expressed. Furthermore, disruption of Tlx-2 function leads to early embryonic lethality. Similar to BMP4 and ALK3 mutants, the mutant embryos display severe defects in primitive streak and mesoderm formation. These experiments thus define a BMP/Tlx-2 signalling pathway that is required during early mammalian gastrulation.

Activin Receptors↗