The growth factor activin elicits mesodermal fates when applied to prospective ectodermal cells of the Xenopus blastula stage embryo. Previous experiments with dissociated cells showed that there are at least five different responses separated by closely spaced, sharp dose thresholds. Here we investigate this multithreshold activin response further using probes for genes expressed at early gastrula stages, namely Xbra, goosecoid, noggin, Xwnt-8 and Mix.1. We show that initial dose-response profiles are broad and smooth in contrast to the later threshold-bound patterns. For Xbra, goosecoid and noggin, the later expression ranges are subsets of earlier ones. Unexpectedly, Xwnt-8 is initially induced at high doses only, but later appears only in cells that have received a low dose of activin. Keeping the cells dissociated after activin treatment, rather than allowing them to reaggregate, prevents sustained expression of Xbra and Xwnt-8 but allows that of goosecoid and noggin. However, cell contact is required for sharpening the dose-response threshold of goosecoid. Finally, we show that a previously reported dorsoventral prepattern in the animal cap is also cell-contact dependent and it is not required for the multi-threshold response to activin.

REFERENCES

Ariizumi
T.
,
Sawamura
K.
,
Uchiyama
H.
,
Asashima
M.
(
1991
)
Dose and time-dependent mesoderm induction and outgrowth formation by activin A in Xenopus laevis.
Int. J. Dev. Biol
35
,
407
14
Blumberg
B.
,
Wright
C. V.
,
De Robertis
E. M.
,
Cho
K. W.
(
1991
)
Organizer-specific homeobox genes in Xenopus laevis embryos.
Science
253
,
194
6
Bögler
O.
,
Entwistle
A.
,
Kuhn
R.
,
Monuki
E.
,
Lemke
G.
,
Noble
M.
(
1993
)
Single cell analysis of the expression of a nuclear protein, SCIP, by fluorescent immunohistochemistry visualized with confocal microscopy.
Histochem. J
25
,
746
761
Bolce
M. E.
,
Hemmati-Brivanlou
A.
,
Kushner
P. D.
,
Harland
R. M.
(
1992
)
Ventral ectoderm of Xenopus forms neural tissue, including hindbrain, in response to activin.
Development
115
,
681
8
Cho
K. W.
,
Blumberg
B.
,
Steinbeisser
H.
,
De Robertis
E. M.
(
1991
)
Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid.
Cell
67
,
1111
20
Christian
J. L.
,
McMahon
J. A.
,
McMahon
A. P.
,
Moon
R. T.
(
1991
)
Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis.
Development
111
,
1045
55
Christian
J. L.
,
Moon
R. T.
(
1993
)
Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus.
Genes Dev
7
,
13
28
Cooke
J.
(
1983
)
Evidence for specific feedback signals underlying pattern control during vertebrate embryogenesis.
J. Embryol. Exp. Morph
76
,
95
114
Cooke
J.
,
Smith
J. C.
,
Smith
E. J.
,
Yagoob
M.
(
1987
)
The organization of mesodermal pattern in Xenopus laevis: experiments using a Xenopus mesoderm-inducing factor.
Development
101
,
893
908
Cornell
R. A.
,
Kimelman
D.
(
1994
)
Activin-mediated mesoderm induction requires FGF.
Development
120
,
453
462
Dale
L.
,
Howes
G.
,
Price
B. M.
,
Smith
J. C.
(
1992
)
Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development.
Development
115
,
573
85
Dale
L.
,
Slack
J. M.
(
1987
)
Regional specification within the mesoderm of early embryos of Xenopus laevis.
Development
100
,
279
95
Driever
W.
,
Nusslein-Volhard
C.
(
1989
)
The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo.
Nature
337
,
138
43
Grainger
R. M.
,
Gurdon
J. B.
(
1989
)
Loss of competence in amphibian induction can take place in single nondividing cells.
Proc. Natl. Acad. Sci. USA
86
,
1900
4
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
83
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
,
731
9
Green
J. 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.
,
Smith
J. C.
(
1991
)
Growth factors as morphogens: do gradients and thresholds establish body plan?.
Trends Genet
7
,
245
50
Grunz
H.
,
Tacke
L.
(
1989
)
Neural differentiation of Xenopus laevis ectoderm takes place after disaggregation and delayed reaggregation without inducer.
Cell Differ. Dev
28
,
211
7
Gurdon
J. B.
(
1988
)
A community effect in animal development.
Nature
336
,
772
4
Gurdon
J. B.
,
Brennan
S.
,
Fairman
S.
,
Mohun
T. J.
(
1984
)
Transcription of muscle-specific actin genes in early Xenopus development: nuclear transplantation and cell dissociation.
Cell
38
,
691
700
Gurdon
J. B.
,
Lemaire
P.
,
Kato
K.
(
1993
)
Community effects and related phenomena in development.
Cell
75
,
831
834
Gurdon
J. B.
,
Mohun
T. J.
,
Brennan
S.
,
Cascio
S.
(
1985
)
Actin genes in Xenopus and their developmental control.
J. Embryol. Exp. Morph
89
,
125
36
Hausen
P.
,
Dreyer
C.
(
1981
)
The use of polyacrylamide as an embedding medium for immunohistochemical studies of embryonic tissues.
Stain Technol
56
,
287
93
Hemmati-Brivanlou
A.
,
Melton
D. A.
(
1992
)
A truncated activin receptor inhibits mesoderm induction and formation of axial structures in Xenopus embryos.
Nature
359
,
609
14
Ip
Y. T.
,
Levine
M.
,
Small
S. J.
(
1992
)
The bicoid and dorsal morphogens use a similar strategy to make stripes in the Drosophila embryo.
J. Cell Sci. Supplement
16
,
33
8
Jones
C. M.
,
Lyons
K. M.
,
Lapan
P. M.
,
Wright
C. V.
,
Hogan
B. L.
(
1992
)
DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction.
Development
115
,
639
47
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
Kimelman
D.
,
Christian
J. L.
,
Moon
R. T.
(
1992
)
Synergisticprinciples of development: overlapping patterning systems in Xenopus mesoderm induction.
Development
116
,
1
9
Kinoshita
K.
,
Bessho
T.
,
Asashima
M.
(
1993
)
Competence prepattern in the animal hemisphere of the 8-cell-stage embryo.
Dev. Biol
160
,
276
284
Krieg
P. A.
,
Varnum
S. M.
,
Wormington
W. M.
,
Melton
D. A.
(
1989
)
The mRNA encoding elongation factor 1-alpha (EF-1 alpha) is a major transcript at the midblastula transition in Xenopus.
Dev. Biol
133
,
93
100
LaBonne
C.
,
Whitman
M.
(
1994
)
Mesoderm induction by activin requires FGF mediated intracellular signals.
Development
120
,
463
472
Lamb
T. M.
,
Knecht
A. K.
,
Smith
W. S.
,
Stachel
S. E.
,
Economides
A. N.
,
Stahl
N.
,
Yancopolous
G. D.
,
Harland
R. M.
(
1993
)
Neural induction by the secreted polypeptide noggin.
Science
262
,
713
718
Lettice
L. A.
,
Slack
J. M. W.
(
1993
)
Properties of the dorsalizing signal in gastrulae of Xenopus laevis.
Development
117
,
263
271
Moon
R. T.
,
Christian
J. L.
(
1992
)
Competence modifiers synergize with growth factors during mesoderm induction and patterning in Xenopus.
Cell
71
,
709
12
Rosa
F. M.
(
1989
).
Mix.1, a homeobox mRNA inducible by mesoderm inducers, is expressed mostly in the presumptive endodermal cells of Xenopus embryos.
Cell
57
,
965
974
Ruiz i Altaba
A.
,
Jessell
T. M.
(
1991
)
Retinoic acid modifies the pattern of cell differentiation in the central nervous system of neurula stage Xenopus embryos.
Development
112
,
945
58
Sargent
M. G.
,
Bennett
M. F.
(
1990
)
Identification in Xenopus of a structural homologue of the Drosophila gene snail.
Development
109
,
967
73
Sargent
T. D.
,
Jamrich
M.
,
Dawid
I. B.
(
1986
)
Cell interactions and the control of gene activity during early development of Xenopus laevis.
Dev. Biol
114
,
238
46
Sive
H. L.
(
1993
)
The frog prince-ss: a molecular formula for dorsoventral patterning in Xenopus.
Genes Dev
7
,
1
12
Smith
J. C.
(
1993
)
Mesoderm inducing factors in early vertebrate development.
EMBO J
12
,
4463
4470
Smith
J. C.
,
Cooke
J.
,
Green
J. B. A.
,
Howes
G.
,
Symes
K.
(
1989
)
Inducing factors and the control of mesodermal pattern in Xenopuslaevis.
Development
107
,
149
59
Smith
J. C.
,
Price
B. M.
,
Van Nimmen
K.
,
Huylebroeck
D.
(
1990
)
Identification of a potent Xenopus mesoderm-inducing factor as a homologueM of activin A.
Nature
345
,
729
31
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 Xenopuslaevis.
J. Embryol. Exp. Morph
78
,
299
317
Smith
J. C.
,
Watt
F. M.
(
1985
)
Biochemical specificity of Xenopus notochord.
Differentiation
29
,
109
15
Smith
W. C.
,
Harland
R. M.
(
1991
)
Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center.
Cell
67
,
753
765
Smith
W. C.
,
Harland
R. M.
(
1992
)
Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos.
Cell
70
,
829
40
Smith
W. C.
,
Knecht
A. K.
,
Wu
M.
,
Harland
R. M.
(
1993
)
Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm.
Nature
361
,
547
9
Sokol
S.
,
Melton
D. A.
(
1991
)
Pre-existent pattern in Xenopus animal pole cells revealed by induction with activin.
Nature
351
,
409
11
St Johnston
D.
,
Nusslein-Volhard
C.
(
1992
)
The origin of pattern and polarity in the Drosophila embryo.
Cell
68
,
201
19
Stewart
R. M.
,
Gerhart
J. C.
(
1990
)
The anterior extent of dorsal development of the Xenopus embryonic axis depends on the quantity of organizer in the late blastula.
Development
109
,
363
72
Symes
K.
,
Yaqoob
M.
,
Smith
J. C.
(
1988
)
Mesoderm induction in Xenopuslaevis: responding cells must be in contact for mesoderm formation but suppression of epidermal differentiation can occur in single cells.
Development
104
,
609
18
Thomsen
G.
,
Woolf
T.
,
Whitman
M.
,
Sokol
S.
,
Vaughan
J.
,
Vale
W.
,
Melton
D. A.
(
1990
)
Activins are expressed early in Xenopus embryogenesis and can induce axialJ mesoderm and anterior structures.
Cell
63
,
485
93
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
4
Wolpert
L.
(
1969
)
Positional information and the spatial pattern of cellular differentiation.
J. Theor. Biol
25
,
1
47
Wright
C. V.
,
Morita
E. A.
,
Wilkin
D. J.
,
De Robertis
E. M.
(
1990
)
The Xenopus XIHbox 6 homeo protein, a marker of posterior neural induction, is expressed in proliferating neurons.
Development
109
,
225
34
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