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.

REFERENCES

Amaya
E.
,
Musci
T. J.
,
Kirschner
M. W.
(
1991
)
Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos.
Cell
66
,
257
70
Amaya
E.
,
Stein
P. A.
,
Musci
T. J.
,
Kirschner
M. W.
(
1993
)
FGF signaling in the early specification of mesoderm in Xenopus.
Development
118
,
477
487
Blumberg
B.
,
Wright
C. V. E.
,
De Robertis
E. M.
,
Cho
K. W. Y.
(
1991
)
Organizer-specific homeobox genes in Xenopus laevis embryos.
Science
253
,
194
196
Cho
K. W. Y.
,
Blumberg
B.
,
Steinbesser
H.
,
De Robertis
E. M.
(
1991
)
Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid.
Cell
67
,
1111
1120
Christian
J. L.
,
McMahon
J. A.
,
McMahon
A. P.
,
Moon
R. T.
(
1991
)
Xwnt −8, a XenopusWnt −1/ int −1-related gene responsive to mesoderm inducing factors, may play a role in ventral mesodermal patterning during embryogenesis.
Development
111
,
1045
56
Christian
J. L.
,
Olson
D. J.
,
Moon
R. T.
(
1992
)
Xwnt −8 modifies the character of mesoderm induced by bFGF in isolated Xenopus ectoderm.
EMBO J
11
,
33
41
Dale
L.
,
Howes
G.
,
Price
B. M. J.
,
Smith
J. C.
(
1992
)
Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development.
Development
115
,
573
585
Frank
D.
,
Harland
R. M.
(
1991
)
Transient expression of XMyoD in non-somite mesoderm of Xenopus gastrulae.
Development
113
,
1387
1393
Green
B. A.
,
Smith
J. C.
(
1990
)
Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate.
Nature
347
,
391
394
Green
J. B. A.
,
Howes
G.
,
Symes
K.
,
Cooke
J.
,
Smith
J. C.
(
1990
)
The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF.
Development
108
,
173
183
Green
J. B. A.
,
New
H. V.
,
Smith
J. C.
(
1992
)
Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm.
Cell
71
,
1
20
Hopwood
N. D.
,
Pluck
A.
,
Gurdon
J. B.
(
1989
)
MyoD expression in the forming somites is an early response to mesoderm induction in Xenopus embryos.
EMBO
8
,
3409
3417
Isaacs
H. V.
,
Tannahill
D.
,
Slack
J. M. W.
(
1992
)
Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification.
Development
114
,
711
720
Jonas
E.
,
Sargent
T. D.
,
Dawid
I. B.
(
1985
)
Epidermal keratin gene expressed in embryos of Xenopus laevis.
Proc. Natl. Acad. Sci. USA
82
,
5413
5417
Jones
C. M.
,
Lyons
K. M.
,
Lapan
P. M.
,
Wright
C. V. E.
,
Hogan
B. L. M.
(
1992
)
DVR-4 (bone morphogenetic protein-4) as a posterior ventralizing factor in Xenopus mesoderm induction.
Development
115
,
639
647
Kimelman
D.
,
Abraham
J. A.
,
Haaparanta
T.
,
Palisi
T. M.
,
Kirschner
M.
(
1988
)
The presence of FGF in the frog egg: its role as a natural mesoderm inducer.
Science
242
,
1053
1056
Kimelman
D.
,
Christian
J. L.
,
Moon
R. T.
(
1992
)
Synergistic principles of development: overlapping patterning systems in Xenopus mesoderm induction.
Development
116
,
1
9
Kimelman
D.
,
Kirschner
M.
(
1987
)
Synergistic induction of mesoderm by FGF and TGF-β and the identification of an mRNA coding for FGF in the early Xenopus embryo.
Cell
51
,
869
877
Kintner
C. R.
,
Melton
D. A.
(
1987
)
Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction.
Development
99
,
311
–.
Krieg
P.
,
Melton
D.
(
1984
)
Functional messenger RNAs are produced by SP6 in vitro transcription of cloned DNAs.
Nucl. Acids Res
12
,
7057
7070
Krieg
P. A.
,
Melton
D. A.
(
1985
)
Developmental regulation of a gastrula-specific gene injected into fertilized Xenopus eggs.
EMBO J
4
,
3463
3471
Krieg
P. A.
,
Varnum
S.
,
Wormington
M. W.
,
Melton
D. A.
(
1989
)
The mRNA encoding elongation factor 1-(EF-1) is a major transcript of the midblastula transition.
Dev. Biol
133
,
93
100
LaBonne
C.
,
Whitman
M.
(
1994
)
Mesoderm induction by activin requires FGF mediated intracellular signals.
Development
120
,
Lee
P. L.
,
Johnson
D. E.
,
Cousens
L. S.
,
Fried
V. A.
,
Williams
L. T.
(
1989
).
Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor.
Science
245
,
57
60
MacNicol
A. M.
,
Muslin
A. J.
,
Williams
L. T.
(
1993
)
Raf-1 kinase is essential for early Xenopus development and mediates the induction of mesoderm by FGF.
Cell
73
,
571
584
Melton
D. A.
,
Krieg
P. A.
,
Rebagliati
M. R.
,
Maniatis
T.
,
Zinn
K.
,
Green
M. R.
(
1984
)
Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
Nucl. Acids Res
12
,
7035
7056
Mohun
T. J.
,
Brennan
S.
,
Dathan
N.
,
Fairman
S.
,
Gurdon
J. B.
(
1984
)
Cell type-specific activation of actin genes in the early amphibian embryo.
Nature
311
,
716
721
Newport
J.
,
Kirschner
M. W.
(
1982
)
A major developmental transition in early Xenopus embryos. I. Characterization and timing of cellular changes at the midblastula stage.
Cell
30
,
675
686
Northrop
J.
,
Kimelman
D.
(
1993
)
Dorsal-ventral differences in response to FGF mediated induction in Xenopus.
Dev. Biol.
in press,
Sargent
M. G.
,
Bennett
M. F.
(
1990
).
Identification in Xenopus of a structural homologue of the Drosophila gene Snail.
Development
109
,
967
973
Sive
H. L.
(
1993
)
The frog prince-cess: A molecular formula for dorsoventral patterning in Xenopus.
Genes Dev
7
,
1
12
Slack
J. M. W.
,
Isaacs
H. V.
(
1989
)
Presence of basic fibroblast growth factor in the early Xenopus embryo.
Development
105
,
147
153
Smith
J. C.
,
Price
B. M. J.
,
Green
J. B. A.
,
Weigel
D.
,
Herrmann
B. G.
(
1991
)
Expression of a Xenopus homolog of brachyury (T) is an immediate-early response to mesoderm induction.
Cell
67
,
79
87
Smith
J. C.
,
Slack
J. M.
(
1983
)
Dorsalization and neural induction: properties of the organizer in Xenopus laevis.
J. Embryol. Exp. Morph
78
,
299
317
Smith
J. C.
,
Symes
K.
,
Hynes
R. O.
,
DeSimone
D.
(
1990
)
Mesoderm induction and the control of gastrulation in Xenopus laevis: the roles of fibronectin and integrins.
Development
108
,
229
238
Smith
W. C.
,
Harland
R. M.
(
1991
)
Injected Xwnt −8 acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center.
Cell
67
,
753
766
Smith
W. C.
,
Harland
R. M.
(
1992
)
Expression cloning of noggin, a new dorsalizing factor localized in the Spemann organizer in Xenopus embryos.
Cell
70
,
829
840
Sokol
S. Y.
,
Melton
D. A.
(
1992
)
Interaction of Wnt and activin in dorsal mesoderm induction in Xenopus.
Dev. Biol
154
,
348
55
Taira
M.
,
Jamrich
M.
,
Good
P. J.
,
Dawid
I. B.
(
1992
)
The LIM domain-containing homeobox gene Xlim-1 is expressed specfically in the organizer region of Xenopus gastrula embryos.
Genes Dev
6
,
356
366
Tannahill
D.
,
Isaacs
H. V.
,
Close
M. J.
,
Peters
G.
,
Slack
J. M. W.
(
1992
)
Developmental expression of the Xenopusint −2 (FGF-3) gene: activation by mesodermal and neural induction.
Development
115
,
695
702
Ullrich
A.
,
Schlessinger
J.
(
1990
)
Signal transduction by receptors with tyrosine kinase activity.
Cell
61
,
203
212
von Dassow
G.
,
Schmidt
J. E.
,
Kimelman
D.
(
1993
)
Induction of the Xenopus organizer: expression and regulation of Xnot, a novel FGF and activin-regulated homeobox gene.
Genes Dev
7
,
355
366
Whitman
M.
,
Melton
D. A.
(
1992
)
Involvement of p21rasin Xenopus mesoderm induction.
Nature
357
,
252
254
This content is only available via PDF.