Mesoderm induction by fibroblast growth factor in early Xenopus development

1990 ◽  
Vol 327 (1239) ◽  
pp. 75-84 ◽  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Marginal Zone ◽  
Mesoderm Induction ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Cell Stage ◽  
Animal Pole

In early amphibian development the mesoderm is formed around the equator of the blastula in response to inductive signals from the endoderm. At the time of its formation the mesoderm consists of a large ‘ventral type’ zone and a small ‘organizer’ zone. A screen of candidate substances showed that a small group of heparin binding growth factors (HBGFs) were active as mesoderm inducing agents in vitro . The fibroblast growth factors (aFGF and bFGF) and embryonal carcinoma derived growth factor (ECDGF) all show similar potency and can produce ventral inductions at concentrations above about 100 pM. Single blastula ectoderm cells can be induced and will differentiate in a defined medium to form mesodermal tissues and all inner blastula cells are competent to respond to the factors. Inducing activity can be extracted from Xenopus blastulae and can be purified by heparin affinity chromatography. Antibody neutralization and Western blotting experiments identify this activity as bFGF. The amounts present are small but would be sufficient to evoke ventral inductions in vivo. It is not yet known whether the bFGF is localized to the endoderm, although it is known that inducing activity secreted by endodermal cells can be neutralized by heparin. The competence of ectoderm to respond to FGF rises from about the 128-cell-stage and falls again by the onset of gastrulation. This change is paralleled by a rise and fall of binding of 125I-labelled aFGF. Chemical cross-linking reveals that this binding is attributable to a receptor of molecular mass about 130 kilodaltons (kDa). The receptor is present both in the marginal zone, which responds to the signal in vivo, and in the animal pole region, which is not induced in vivo but which will respond to HBGFs in vitro . In intact embryos we believe that the ventral type mesoderm forms the somites, kidney and other intermediate structures as well as the blood islands of the ventral midline. These intermediate structures are induced as a function of distance from the organizer in a process called ‘dorsalization’. Lithium salts have a dorsalizing effect on whole embryos and also on explants from the ventral marginal zone, causing them to form large blocks of muscle. Lithium will also cause large muscle blocks to form when applied to ectoderm explants together with FGF. It is difficult to extend these results directly to mammalian embryos, but we have shown that the products of the murine int-2 gene and of the human k-fgf genes are active as mesoderm inducing factors.

The role of fibroblast growth factor in early Xenopus development

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 141-148 ◽  
Author(s):  
J. M. W. Slack ◽  
B. G. Darlington ◽  
L. L. Gillespie ◽  
S. F. Godsave ◽  
H. V. Isaacs ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Specific Activity ◽  
Progressive Increase ◽  
Defined Medium ◽  
Relative Molecular Mass ◽  
Heparin Binding ◽  
Cell Stage ◽  
Animal Pole

In early amphibian development, the mesoderm is formed around the equator of the blastula in response to an inductive signal from the endoderm. A screen of candidate substances showed that a small group of heparin-binding growth factors (HBGFs) were active as mesoderm-inducing agents in vitro. The factors aFGF, bFGF, kFGF and ECDGF all show similar potency and can produce inductions at concentrations above about 100 pM. The product of the murine int-2 gene is also active, but with a lower specific activity. Above the induction threshold there is a progressive increase of muscle formation with dose. Single blastula ectoderm cells can be induced and will differentiate in a defined medium to form mesodermal tissues. All inner blastula cells are competent to respond to the factors but outer cells, bearing oocyte-derived membrane, are not. Inducing activity can be extracted from Xenopus blastulae and binds to heparin like the previously described HBGFs. Antibody neutralization and Western blotting experiments identify this activity as bFGF. The amounts present are small but would be sufficient to evoke inductions in vivo. It is not yet known whether the bFGF is localized to the endoderm, although it is known that inducing activity secreted by endodermal cells can be neutralized by heparin. The competence of ectoderm to respond to HBGFs rises from about the 128-cell stage and falls again by the onset of gastrulation. This change is paralleled by a rise and fall of binding of 125I-aFGF. Chemical cross-linking reveals that this binding is attributable to a receptor of relative molecular mass about 130 × 103. The receptor is present both in the marginal zone, which responds to the signal in vivo, and in the animal pole region, which is not induced in vivo but which will respond to HBGFs in vitro. In the embryo, the induction in the vicinity of the dorsal meridian is much more potent than that around the remainder of the marginal zone circumference. Dorsal inductions contain notochord and will dorsalize ventral mesoderm with which they are later placed in contact. This effect might be due to a local high bFGF concentration or, more likely, to the secretion in the dorsal region of an additional, synergistic factor. It is known that TGF-β-1 and -2 can greatly increase the effect of low doses of bFGF, although it has not yet been demonstrated that they are present in the embryo. Lithium salts have a dorsalizing effect on whole embryos or on explants from the ventral marginal zone, and also show potent synergism when applied together with HBGFs.

scholarly journals Growth factors are released by mechanically wounded endothelial cells.

1989 ◽  
Vol 109 (2) ◽  
pp. 811-822 ◽  
Author(s):  
P L McNeil ◽  
L Muthukrishnan ◽  
E Warder ◽  
P A D'Amore
Keyword(s):  
Endothelial Cells ◽  
Plasma Membrane ◽  
Growth Factors ◽  
Growth Factor ◽  
Mechanical Forces ◽  
Fibroblast Growth ◽  
Growth Promoting ◽  
Transient Plasma

Growth factors may be required at sites of mechanical injury and normal wear and tear in vivo, suggesting that the direct action of mechanical forces on cells could lead to growth factor release. Scraping of cells from the tissue culture substratum at 37 degrees C was used to test this possibility. We show that scraping closely mimics in vitro both the transient plasma membrane wounds observed in cells subject to mechanical forces in vivo (McNeil, P. L., and S. Ito. 1989. Gastroenterology. 96:1238-1248) and the transient plasma membrane wounds shown here to occur in endothelial cells under normal culturing conditions. Scraping of endothelial cells from the culturing substratum released into the culture medium a potent growth-promoting activity for Swiss 3T3 fibroblasts. Growth-promoting activity was released rapidly (within 5 min) after scraping but was not subsequently degraded by the endothelial cells for at least 24 h thereafter. A greater quantity of growth-promoting activity was released by cells scraped 4 h after plating than by those scraped 4 or 7 d afterwards. Thus release is not due to scraping-induced disruption of extracellular matrix. Release was only partially cold inhibitable, was poorly correlated with the level of cell death induced by scraping, and did not occur when cells were killed with metabolic poisons. These results suggest that mechanical disruption of plasma membrane, either transient or permanent, is the essential event leading to release. A basic fibroblast growth factor-like molecule and not platelet-derived growth factor appears to be partially responsible for the growth-promoting activity. We conclude that one biologically relevant route of release of basic fibroblast growth factor, a molecule which lacks the signal peptide sequence for transport into the endoplasmic reticulum, could be directly through mechanically induced membrane disruptions of endothelial cells growing in vivo and in vitro.

Basic fibroblast growth factor induces notochord formation and the expression of As-T, a Brachyury homolog, during ascidian embryogenesis

Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 2023-2031 ◽  
Author(s):  
Y. Nakatani ◽  
H. Yasuo ◽  
N. Satoh ◽  
H. Nishida
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Mesoderm Induction ◽  
Fibroblast Growth ◽  
Halocynthia Roretzi ◽  
Cell Stage ◽  
Inductive Interaction ◽  
Notochord Cells

The tadpole larva of an ascidian develops 40 notochord cells in the center of its tail. Most of the notochord cells originate from the A-line precursors, among which inductive interactions are required for the subsequent differentiation of notochord. The presumptive-endoderm blastomeres or presumptive-notochord blastomeres themselves are inducers of notochord formation. Notochord induction takes place during the 32-cell stage. In amphibia, mesoderm induction is thought to be mediated by several growth factors, for example, activins and basic fibroblast growth factor (bFGF). In the ascidian, Halocynthia roretzi, treatment with bFGF of presumptive-notochord blastomeres that had been isolated at the early 32-cell stage promoted the formation of notochord at a low concentration of bFGF (0.02 ng/ml), while activin failed to induce notochord differentiation. The effect of bFGF reached a maximum at the end of the 32-cell stage and rapidly faded at the beginning of the subsequent cleavage, the time for full induction of notochord being at least 20 minutes. The expression of As-T, a previously isolated ascidian homolog of the mouse Brachyury (T) gene, starts at the 64-cell stage and is detectable exclusively in the presumptive-notochord blastomeres. The present study showed that presumptive-notochord blastomeres, isolated at the early 32-cell stage, neither differentiated into notochord nor expressed the As-T gene. However, when the presumptive-notochord blastomeres were coisolated or recombined with inducer blastomeres, transcripts of As-T were detected. When presumptive-notochord blastomeres were treated with bFGF, the expression of the As-T gene was also detected. These results suggest that inductive interaction is required for the expression of the As-T gene and that the expression of the As-T gene is closely correlated with the determined state of the notochord-precursor cells.

scholarly journals Growth factors and goitrogenesis

1999 ◽  
Vol 160 (3) ◽  
pp. 321-332 ◽  
Author(s):  
SP Bidey ◽  
DJ Hill ◽  
MC Eggo
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibroblast Growth Factors ◽  
In Vitro Models ◽  
Fibroblast Growth ◽  
Paracrine Factors ◽  
Combining Data ◽  
Paracrine Actions

By combining data from studies of multinodular non-toxic goitre (MNTG) with data from rat models of goitre induction and in vitro models, a map of the growth factors involved in goitrogenesis has been constructed. We have addressed the roles of the insulin-like growth factors, transforming growth factors, fibroblast growth factors, endothelins, etc. We hypothesise that an imbalance in the interactions between the various growth factor axes exists in MNTG which favours cell replication. Thyrotrophin, although not significantly elevated in MNTG, exerts critical effects through interactions with autocrine and paracrine factors and their receptors. Expansion of the thyroidal vascular bed through angiogenesis is closely co-ordinated with follicular cell expansion and folliculoneogenesis, and while the integrated paracrine actions of fibroblast growth factors, vascular endothelial growth factor and endothelin probably play central roles, additional, as yet elusive, factors are probably involved. The combination of in vitro and in vivo approaches, designed to address specific questions, will undoubtedly continue to prove invaluable in dissecting further the complex interactions that exist between these growth factors, their binding proteins and receptors in goitrogenesis.

scholarly journals Dynamic changes of podocytes caused by fibroblast growth factor 2 in culture

2021 ◽  
Author(s):  
Eishin Yaoita ◽  
Masaaki Nameta ◽  
Yutaka Yoshida ◽  
Hidehiko Fujinaka
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 2 ◽  
Quiescent State ◽  
Fibroblast Growth ◽  
Gene Expressions ◽  
Dynamic Changes ◽  
Ki 67

AbstractFibroblast growth factor 2 (FGF2) augments podocyte injury, which induces glomerulosclerosis, although the mechanisms remain obscure. In this study, we investigated the effects of FGF2 on cultured podocytes with interdigitating cell processes in rats. After 48 h incubation with FGF2 dynamic changes in the shape of primary processes and cell bodies of podocytes resulted in the loss of interdigitation, which was clearly shown by time-lapse photography. FGF2 reduced the gene expressions of constituents of the slit diaphragm, inflections of intercellular junctions positive for nephrin, and the width of the intercellular space. Immunostaining for the proliferation marker Ki-67 was rarely seen and weakly stained in the control without FGF2, whereas intensely stained cells were frequently found in the presence of FGF2. Binucleation and cell division were also observed, although no significant increase in cell number was shown. An in vitro scratch assay revealed that FGF2 enhanced migration of podocytes. These findings show that FGF2 makes podocytes to transition from the quiescent state into the cell cycle and change their morphology due to enhanced motility, and that the culture system in this study is useful for analyzing the pathological changes of podocytes in vivo.

Evaluation of the bioactivity about anti-sca-1/basic fibroblast growth factor-urinary bladder matrix scaffold for pelvic reconstruction

2018 ◽  
Vol 33 (6) ◽  
pp. 808-818 ◽  
Author(s):  
Jiankui Li ◽  
Xi Chen ◽  
Kaijian Ling ◽  
Zhiqing Liang ◽  
Huicheng Xu
Keyword(s):  
Growth Factor ◽  
Urinary Bladder ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Pelvic Organ ◽  
Fibroblast Growth ◽  
Pelvic Reconstruction ◽  
Urinary Bladder Matrix

Introduction and hypothesis: Pelvic support structure injury is the major cause of pelvic organ prolapse. At present, polypropylene-based filler material has been suggested as a common method to treat pelvic organ prolapse. However, it cannot functionally rehabilitate the pelvic support structure. In addition to its poor long-term efficiency, the urinary bladder matrix was the most suitable biological scaffold material for pelvic floor repair. Here, we hypothesize that anti-sca-1 monoclonal antibody and basic fibroblast growth factor were cross-linked to urinary bladder matrix to construct a two-factor bioscaffold for pelvic reconstruction. Methods Through a bispecific cross-linking reagent, sulfosuccinimidyl 4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-smcc) immobilized anti-sca-1 and basic fibroblast growth factor to urinary bladder matrix. Then scanning electron microscope and plate reader were used to detect whether the anti-sca-1/basic fibroblast growth factor-urinary bladder matrix scaffold was built successfully. After that, the capacity of enriching sca-1 positive cells was measured both in vitro and in vivo. In addition, we evaluated the differentiation capacity and biocompatibility of the scaffold. Finally, western blotting was used to detect the level of fibulin-5 protein. Results The scanning electron microscope and plate reader revealed that the double-factor biological scaffold was built successfully. The scaffold could significantly enrich a large number of sca-1 positive cells both in vitro and in vivo, and obviously accelerate cells and differentiate functional tissue with good biocompatibility. Moreover, the western blotting showed that the scaffold could improve the expression of fibulin-5 protein. Conclusion The anti-sca-1/basic fibroblast growth factor-urinary bladder matrix scaffold revealed good biological properties and might serve as an ideal scaffold for pelvic reconstruction.

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