The first inductive event in Xenopus development establishes the mesoderm at the equator of the developing embryo. As part of this process, the dorsal-ventral and anterior-posterior axes of the embryo are initially established. A number of signalling molecules which may play a role in mesodermal induction and patterning have been identified in the last several years, including members of the FGF, TGF-beta and Wnt gene families. A variety of experiments, using either purified factors or injection of RNA encoding these factors, have added to the wealth of classical embryogical experimental data collected over the last century. We have synthesized some recent results with the classical data to provide a framework for examining the process of mesoderm induction, and to formulate putative roles for some of the different factors. We incorporate these ideas into a working model of mesoderm induction that provides a basis for future experimental directions. Finally, we suggest that mesoderm induction may not be a discrete set of well separated events, but instead may be a process involving partially overlapping signals that produce the same pattern.

REFERENCES

Albano
R. M.
,
Godsave
S. F.
,
Huylebroeck
D.
,
Van Nimmen
K.
,
Isaacs
H. V.
,
Slack
J. M. W.
,
Smith
J. C.
(
1990
)
A mesoderm-inducing factor produced by WEHI-3 murine myelomonocytic leukemia cells is activin A.
Development
110
,
435
443
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
270
Asashima
M.
,
Nakano
H.
,
Ucimaya
H.
,
Sugino
H.
,
Nakamura
T.
,
Eto
Y.
,
Ejima
D.
,
Nisimatsu
S.
,
Ueno
N.
,
Kinoshita
K.
(
1991
)
Presence of activin (erythroid differentiation factor) in unfertilized eggs and blastulae of Xenopus laevis.
Proc. Natl. Acad. Sci. USA
88
,
6511
6514
Chisaka
O.
,
Capecchi
M. R.
(
1991
).
Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5.
Nature
350
,
473
479
Cho
K. W. Y.
,
De Robertis
E. M.
(
1990
)
Differential activation of Xenopus homeobox genes by mesoderm-inducing growth factors and retinoic acid.
Genes Dev
4
,
1910
1916
Christian
J. L.
,
Gavin
B. J.
,
McMahon
A. P.
,
Moon
R. T.
(
1991
)
Isolation of cDNAs partially encoding four XenopusWnt −1/ int −1-related proteins and characterization of their transient expression during embryonic development.
Dev. Biol
143
,
230
234
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
1056
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
Cooke
J.
(
1989
)
Mesoderm inducing factors and Spemann's organiser phenomenon in amphibian development.
Development
107
,
229
241
Dale
L.
,
Slack
J. M.
(
1987
)
Fate map for the 32-cell stage of Xenopus laevis.
Development
99
,
527
551
Dale
L.
,
Slack
J. M. W.
(
1987
)
Regional specification within the mesoderm of early embryos of Xenopus laevis.
Development
100
,
279
295
Dale
L.
,
Smith
J. C.
,
Slack
J. M.
(
1985
)
Mesoderm induction in Xenopus laevis: a quantitative study using a cell lineage label and tissue-specific antibodies.
J. Embryol. exp. Morph
89
,
289
312
Friesel
R.
,
Dawid
I. B.
(
1991
)
cDNA cloning and developmental expression of fibroblast growth factor receptors from Xenopus laevis.
Mol. Cell. Biol
11
,
2481
2488
Gallagher
B. C.
,
Hainski
A. M.
,
Moody
S. A.
(
1991
)
Autonomous differentiation of dorsal axial structures from an animal cap cleavage stage blastomere in Xenopus.
Development
112
,
1103
1114
Gillespie
L. L.
,
Paterno
G. D.
,
Slack
J. M.
(
1989
)
Analysis of competence: receptors for fibroblast growth factor in early Xenopus embryos.
Development
106
,
203
208
Gimlich
R. L.
(
1986
)
Acquisition of developmental autonomy in the equatorial region of the Xenopus embryo.
Dev. Biol
115
,
340
352
Grant
P.
,
Wacaster
J. F.
(
1972
)
The amphibian gray crescent region- a site of developmental information?.
Dev. Biol
28
,
454
471
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
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
Joyner
A. L.
,
Herrup
K.
,
Auerbach
B. A.
,
Davis
C. A.
,
Rossant
J.
(
1991
)
Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox.
Science
251
,
1239
1243
Kageura
H.
(
1990
)
Spatial distribution of the capacity to initiate a secondary embryo in the 32-cell embryo of Xenopus laevis.
Dev. Biol
142
,
432
438
Kageura
H.
,
Yamana
K.
(
1984
)
Pattern regulation in defect embryos of Xenopus laevis.
Dev. Biol
101
,
410
415
Kageura
H.
,
Yamana
K.
(
1986
)
Pattern formation in 8-cell composite embryos of Xenopus laevis.
J. Embryol. exp. Morphol
91
,
79
100
Kaneda
T.
(
1981
)
Studies of the formation and state of determination of the trunk organizer in the newt, Cynops pyrrhogaster, III. Tangential induction in the dorsal marginal zone.
Dev. Growth and Differ
23
,
553
564
Kao
K.
,
Elinson
R. P.
(
1989
)
Dorsalization of mesoderm induction by lithium.
Dev. Biol
132
,
81
90
Kao
K. R.
,
Elinson
R. P.
(
1988
)
The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.
Dev. Biol
127
,
64
77
Kao
K. R.
,
Masui
Y.
,
Elinson
R. P.
(
1986
)
Lithium induced respecification of pattern in Xenopus laevis embryos.
Nature
322
,
371
373
Keller
R.
,
Tibbetts
P.
(
1989
)
Mediolateral cell intercalation in the dorsal, axial mesoderm of Xenopus laevis.
Dev. Biol
131
,
539
549
Keller
R. E.
(
1976
)
Vital dye mapping of the gastrula and neurula of Xenopus laevis.
Dev. Biol
51
,
118
137
Kimelman
D.
,
Abraham
J. A.
,
Haaparanta
T.
,
Palisi
T. M.
,
Kirschner
M. W.
(
1988
)
The presence of fibroblast growth factor in the frog egg: its role as a natural mesoderm inducer.
Science
242
,
1053
1056
Kimelman
D.
,
Kirschner
M.
(
1987
)
Synergistic induction of mesoderm by FGF and TGF-and the indentification of an mRNA coding for FGF in the early Xenopus embryo.
Cell
51
,
869
877
Kimelman
D.
,
Maas
A.
(
1992
)
Induction of dorsal and ventral mesoderm by ectopically expressed Xenopus basic fibroblast growth factor.
Development
114
,
261
269
Kintner
C. R.
,
Dodd
J.
(
1991
)
Hensen's node induces neural tissue in Xenopus ectoderm. Implications for the action of the organizer in neural induction.
Development
113
,
1495
1505
Kondo
M.
,
Tashiro
K.
,
Fujii
G.
,
Asano
M.
,
Miyoshi
R.
,
Yamada
R.
,
Muramatsu
M.
,
Shiokawa
K.
(
1991
)
Activin receptor mRNA is expressed early in Xenopus embryogenesis and the level of expression affects the body axis formation.
Biochem. Biophys. Res. Commun
181
,
684
690
Koster
M.
,
Plessow
S.
,
Clement
J. H.
,
Lorenz
A.
,
Tiedemann
H.
,
Knochel
W.
(
1991
)
Bone morphogenetic protein 4 (BMP-4), a member of the TGF- family in early embryos of Xenopus laevis: analysis of mesoderm inducing activity.
Mech. Dev
33
,
191
200
Lufkin
T.
,
Dierich
A.
,
LeMeur
M.
,
Mark
M.
,
Chambon
P.
(
1991
).
Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression.
Cell
66
,
1105
1119
Malacinski
G. M.
,
Brothers
J.
,
Chung
H.-M.
(
1977
)
Destruction of components of the neural induction system of the amphibian egg with ultraviolet irradiation.
Dev. Biol
56
,
24
39
Matthews
L. S.
,
Vale
W. W.
,
Kintner
C. R.
(
1992
)
Cloning of a second type of activin receptor and functional characterization in Xenopus embryos.
Science
255
,
1702
1705
McMahon
A. P.
,
Bradley
A.
(
1990
)
The Wnt −1 (int −1) proto-oncogene is required for development of a large region of the mouse brain.
Cell
62
,
1073
1085
McMahon
A. P.
,
Moon
R. T.
(
1989
)
Ectopic expression of the proto-oncogene int −1 in Xenopus embryos leads to duplication of the embryonic axis.
Cell
58
,
1075
1084
Moody
S. A.
(
1987
)
Fates of the blastomeres of the 16-cell stage Xenopus embryo.
Dev. Biol
119
,
560
578
Moody
S. A.
(
1987
)
Fates of the blastomeres of the 32-cell-stage Xenopus embryo.
Dev. Biol
122
,
300
319
Musci
T. J.
,
Amaya
E.
,
Kirschner
M. W.
(
1990
)
Regulation of the fibroblast growth factor receptor in early Xenopus embryos.
Proc. Natl. Acad. Sci. USA
87
,
8365
8369
Nagajski
D. J.
,
Guthrie
S. C.
,
Ford
C. C.
,
Warner
A. E.
(
1989
).
The correlation between patterns of dye transfer through gap junctions and future developmental fate in Xenopus: the consequences of u.v. irradiation and lithium treatment.
Development
105
,
747
752
Nieuwkoop
P. D.
(
1973
)
The “organization center” of the amphibian embryo: its origin, spatial organization and morphogenetic action.
Advances in Morphogenesis
10
,
1
39
Noordermeer
J.
,
Meijlink
F.
,
Verrijzer
P.
,
Rijsewijk
F.
,
Destree
O.
(
1989
)
Isolation of the Xenopus homolog of int −1/ wingless and expression during neurula stages of early development.
Nucleic Acids Res
17
,
11
18
Olson
D. J.
,
Christian
J. L.
,
Moon
R. T.
(
1991
)
Effect of wnt −1 and related proteins on gap junctional communication in Xenopus embryos.
Science
252
,
1173
1176
Pierce
K. E.
,
Brothers
J. A.
(
1988
)
Dorsal and ventral cells of cleavage stage embryos show the same ability to induce notochord and somite formation.
Dev. Biol
126
,
228
232
Roberts
A. B.
,
Kondaiah
P.
,
Rosa
F.
,
Watanabe
S.
,
Good
P.
,
Roche
N. S.
,
Rebbert
M. L.
,
Dawid
I. B.
,
Sporn
M. B.
(
1990
)
Mesoderm induction in Xenopuslaevis distinguishes between the various TGF- isoforms.
Growth factors
3
,
277
286
Ruiz i Altaba
A.
,
Jessell
T.
(
1991
)
Retinoic acid modifies mesodermal patterning in early Xenopus embryos.
Genes Dev
5
,
175
87
Ruiz i Altaba
A.
,
Melton
D. A.
(
1989
)
Interaction between peptide growth factors and homeobox genes in the establishment of antero-posterior polarity in frog embryos.
Nature
341
,
33
38
Scharf
S. R.
,
Gerhart
J. C.
(
1980
)
Determination of the dorsal-ventral axis in eggs of Xenopus laevis: complete rescue of uv-impaired eggs by oblique orientation before first cleavage.
Dev. Biol
79
,
181
198
Scharf
S. R.
,
Gerhart
J. C.
(
1983
)
Axis determination in eggs of Xenopus laevis: a critical period before first cleavage, indentified by the common effects of cold, pressure, and ultraviolet irradiation.
Dev. Biol
99
,
75
87
Shiurba
R. A.
,
Jing
N.
,
Sakakura
T.
,
Godsave
S. F.
(
1991
)
Nuclear translocation of fibroblast growth factor during Xenopus mesoderm induction.
Development
113
,
487
493
Slack
J. M.
,
Dale
L.
,
Smith
J. C.
(
1984
)
Analysis of embryonic induction by using cell lineage markers.
Philos. Trans. R. Soc. Lond
307
,
331
336
Slack
J. M.
,
Isaacs
H. V.
,
Darlington
B. G.
(
1988
)
Inductive effects of fibroblast growth factor and lithium ion on blastula ectoderm.
Development
103
,
581
590
Slack
J. M. W.
,
Darlington
B. G.
,
Heath
J. K.
,
Godsave
S. F.
(
1987
)
Mesoderm induction in early Xenopus embryos by heparin-binding growth factors.
Nature
326
,
197
200
Slack
J. M. W.
,
Forman
D.
(
1980
)
An interaction between dorsal and ventral regions of the marginal zone in early amphibian embryos.
J. Embryol. exp. Morph
56
,
283
299
Slack
J. M. W.
,
Isaacs
H. V.
(
1989
)
Presence of basic fibroblast growth factor in the early Xenopus embryo.
Development
105
,
147
153
Slack
J. M. W.
,
Tannahill
D.
(
1992
)
Mechanism of anteroposterior axis specification in vertebrates: lessons from the amphibians.
Development
114
,
285
302
Smith
J. C.
(
1987
)
A mesoderm-inducing factor is produced by a Xenopus cell line.
Development
99
,
3
14
Smith
J. C.
,
Dale
L.
,
Slack
J. M. W.
(
1985
)
Cell lineage of labels and region-specific markers in the analysis of inductive interactions.
J. Embryol. exp. Morph
89
,
317
331
Smith
J. C.
,
Price
B. M. J.
,
Van Nimmen
K.
,
Huylebroeck
D.
(
1990
)
Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A.
Nature
345
,
729
731
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
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
Sokol
S.
,
Christian
J. L.
,
Moon
R. T.
,
Melton
D. A.
(
1991
)
Injected wnt RNA induces a complete body axis in Xenopus embryos.
Cell
67
,
741
752
Sokol
S.
,
Melton
D. A.
(
1991
)
Pre-existent pattern in Xenopus animal pole cells revealed by induction with activin.
Nature
351
,
409
411
Sokol
S.
,
Wong
G.
,
Melton
D. A.
(
1990
)
A mouse macrophage factor induces head structure and organizes a body axis in Xenopus.
Science
249
,
561
564
Soriano
P.
,
Montgomery
C.
,
Geske
R.
,
Bradley
A.
(
1991
)
Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice.
Cell
64
,
693
702
Takasaki
H.
,
Konishi
H.
(
1989
)
Dorsal blastomeres in the equatorial region of the 32-cell Xenopus embryo autonomously produce progeny committed to the organizer.
Develop. Growth and Differ
31
,
147
156
Thomas
K. R.
,
Capecchi
M. R.
(
1990
)
Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development.
Nature
346
,
847
850
Thomsen
G.
,
Woolf
T.
,
Whitman
M.
,
Sokol
S.
,
Vaughan
J.
,
Vale
W.
,
Melton
D. A.
(
1990
)
Activins are expressed in Xenopus embryogenesis and can induce axial mesoderm and anterior structures.
Cell
63
,
485
493
van den Eijnden Van Raaij
A. J.
,
van Zoelent
E. J.
,
van Nimmen
K.
,
Koster
C. H.
,
Snoek
G. T.
,
Durston
A. J.
,
Huylebroeck
D.
(
1990
)
Activin-like factor from a Xenopus laevis cell line responsible for mesoderm induction.
Nature
345
,
732
734
Vincent
J. P.
,
Gerhart
J. C.
(
1987
)
Subcortical rotation in Xenopus eggs: an early step in embryonic axis formation.
Dev. Biol
123
,
526
539
Wilson
P. A.
,
Oster
G.
,
Keller
R.
(
1989
)
Cell rearrangement and segmentation in Xenopus: direct observation of cultured explants.
Development
105
,
155
166
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