Activin-mediated mesoderm induction requires FGF

The early patterning of mesoderm in the Xenopus embryo requires signals from several intercellular factors, including mesoderm-inducing agents that belong to the fibroblast growth factor (FGF) and TGF-beta families. In animal hemisphere explants (animal caps), basic FGF and the TGF-beta family member activin are capable of converting pre-ectodermal cells to a mesodermal fate, although activin is much more effective at inducing dorsal and anterior mesoderm than is basic FGF. Using a dominant-negative form of the Xenopus type 1 FGF receptor, we show that an FGF signal is required for the full induction of mesoderm by activin. Animal caps isolated from embryos that have been injected with the truncated FGF receptor and cultured with activin do not extend and the induction of some genes, including cardiac actin and Xbra, is greatly diminished, while the induction of other genes, including the head organizer-specific genes gsc and Xlim-1, is less sensitive. These results are consistent with the phenotype of the truncated FGF receptor-injected embryo and imply that the activin induction of mesoderm depends on FGF, with some genes requiring a higher level of FGF signaling than others.

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FGF signals are involved in the differentiation of notochord cells and mesenchyme cells of the ascidianHalocynthia roretzi

Development ◽

10.1242/dev.128.14.2711 ◽

2001 ◽

Vol 128 (14) ◽

pp. 2711-2721 ◽

Cited By ~ 4

Author(s):

Yoshie Shimauchi ◽

Seiko D. Murakami ◽

Nori Satoh

Keyword(s):

Receptor Gene ◽

Epidermal Cells ◽

Dominant Negative ◽

Tyrosine Kinase Domain ◽

Fgf Receptor ◽

Dominant Negative Form ◽

Notochord Cells ◽

Mesenchyme Cells ◽

Endodermal Cells ◽

Negative Form

Differentiation of notochord cells and mesenchyme cells of the ascidian Halocynthia roretzi requires interactions with neighboring endodermal cells and previous experiments suggest that these interactions require fibroblast growth factor (FGF). In the present study, we examined the role of FGF in these interactions by disrupting signaling using the dominant negative form of the FGF receptor. An FGF receptor gene of H. roretzi (HrFGFR) is expressed both maternally and zygotically. The maternally expressed transcript was ubiquitously distributed in fertilized eggs and in early embryos. Zygotic expression became evident by the neurula stage and transcripts were detected in epidermal cells of the posterior half of embryos. Synthetic mRNA for the dominant negative form of FGFR, in which the intracellular tyrosine kinase domain was deleted, was injected into fertilized eggs to interfere with the possible function of HrFGFR. Injected eggs cleaved and gastrulated the same as the control embryos. Analyses of the expression of differentiation markers in the experimental embryos indicated that the differentiation of epidermal cells, muscle cells and endodermal cells was not affected significantly. However, manipulated embryos showed downregulation of notochord-specific Brachyury expression and failure of notochord cell differentiation, resulting in the development of tailbud embryos with shorted tails. The expression of an actin gene that is normally expressed in mesenchyme cells was also suppressed. These results suggest that FGF signals are involved in differentiation of notochord cells and mesenchyme cells in Halocynthia embryos. Furthermore, the patterning of a neuron-specific tubulin gene expression was disturbed, suggesting that the formation of the nervous system was directly affected by disrupting FGF signals or indirectly affected due to the disruption of normal notochord formation.

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Induction of the mesendoderm in the zebrafish germ ring by yolk cell-derived TGF-beta family signals and discrimination of mesoderm and endoderm by FGF

Development ◽

10.1242/dev.126.14.3067 ◽

1999 ◽

Vol 126 (14) ◽

pp. 3067-3078 ◽

Cited By ~ 18

Author(s):

A. Rodaway ◽

H. Takeda ◽

S. Koshida ◽

J. Broadbent ◽

B. Price ◽

...

Keyword(s):

Ectopic Expression ◽

Dominant Negative ◽

Fibroblast Growth ◽

Tgf Beta ◽

Fgf Receptor ◽

Activin Receptor ◽

Yolk Cell ◽

Endogenous Expression ◽

Vertebrate Embryo ◽

Fgf Signalling

The endoderm forms the gut and associated organs, and develops from a layer of cells which emerges during gastrula stages in the vertebrate embryo. In comparison to mesoderm and ectoderm, little is known about the signals which induce the endoderm. The origin of the endoderm is intimately linked with that of mesoderm, both by their position in the embryo, and by the molecules that can induce them. We characterised a gene, zebrafish gata5, which is expressed in the endoderm from blastula stages and show that its transcription is induced by signals originating from the yolk cell. These signals also induce the mesoderm-expressed transcription factor no tail (ntl), whose initial expression coincides with gata5 in the cells closest to the blastoderm margin, then spreads to encompass the germ ring. We have characterised the induction of these genes and show that ectopic expression of activin induces gata5 and ntl in a pattern which mimics the endogenous expression, while expression of a dominant negative activin receptor abolishes ntl and gata5 expression. Injection of RNA encoding a constitutively active activin receptor leads to ectopic expression of gata5 and ntl. gata5 is activated cell-autonomously, whereas ntl is induced in cells distant from those which have received the RNA, showing that although expression of both genes is induced by a TGF-beta signal, expression of ntl then spreads by a relay mechanism. Expression of a fibroblast growth factor (eFGF) or a dominant negatively acting FGF receptor shows that ntl but not gata5 is regulated by FGF signalling, implying that this may be the relay signal leading to the spread of ntl expression. In embryos lacking both squint and cyclops, members of the nodal group of TGF-beta related molecules, gata5 expression in the blastoderm is abolished, making these factors primary candidates for the endogenous TGF-beta signal inducing gata5.

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Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation

Development ◽

10.1242/dev.122.10.3173 ◽

1996 ◽

Vol 122 (10) ◽

pp. 3173-3183 ◽

Cited By ~ 68

Author(s):

K.L. Kroll ◽

E. Amaya

Keyword(s):

Large Scale ◽

Neural Induction ◽

Dominant Negative ◽

Dominant Negative Mutant ◽

Mesoderm Induction ◽

Fgf Signaling ◽

Fgf Receptor ◽

Transgenic Expression

We have developed a simple approach for large-scale transgenesis in Xenopus laevis embryos and have used this method to identify in vivo requirements for FGF signaling during gastrulation. Plasmids are introduced into decondensed sperm nuclei in vitro using restriction enzyme-mediated integration (REMI). Transplantation of these nuclei into unfertilized eggs yields hundreds of normal, diploid embryos per day which develop to advanced stages and express integrated plasmids nonmosaically. Transgenic expression of a dominant negative mutant of the FGF receptor (XFD) after the mid-blastula stage uncouples mesoderm induction, which is normal, from maintenance of mesodermal markers, which is lost during gastrulation. By contrast, embryos expressing XFD contain well-patterned nervous systems despite a putative role for FGF in neural induction.

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FGF suppresses apoptosis and induces differentiation of fibre cells in the mouse lens

Development ◽

10.1242/dev.121.12.4383 ◽

1995 ◽

Vol 121 (12) ◽

pp. 4383-4393 ◽

Cited By ~ 4

Author(s):

R.L. Chow ◽

G.D. Roux ◽

M. Roghani ◽

M.A. Palmer ◽

D.B. Rifkin ◽

...

Keyword(s):

Growth Factor ◽

Transgenic Mice ◽

Dominant Negative ◽

Fgf Receptor ◽

Fibre Cell ◽

Dominant Negative Form ◽

Lens Fibre ◽

Mouse Lens ◽

Negative Form

To determine whether fibroblast growth factor (FGF) has a role in lens development, we have generated transgenic mice expressing a dominant-negative form of the murine FGF receptor-1 (FGFRDN) in the lens. Using the fibre cell-specific alpha A-crystallin promoter to express the FGFRDN, we have asked whether FGF is required for fibre cell differentiation. The transgenic mice display diminished differentiation of fibre cells as indicated by their reduced elongation. In addition, transgenic lenses have an unusual refractile anomaly that morphological and biochemical data show results from the apoptosis of fibre cells in the central region of the lens. These results show that lens fibre cells are dependent on FGF for their survival and differentiation, and demonstrate that growth factor deprivation in vivo can lead to apoptosis.

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